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Results for “Infiltrative”

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At least 235 records · Page 13Linked to original sources

PubMed2005

Interleukin-4-mediated infiltration of eosinophils into the conjunctiva and its suppression by interferon-gamma.

PURPOSE: Interleukin (IL)-4 is a T helper (Th)2 cytokine that plays an important role in the development of allergic reactions. It has been suggested that IL-4 is responsible for the infiltration of eosinophils into the conjunctiva during the development of allergic conjunctivitis. However, it is still unclear whether IL-4 is able to induce this eosinophilic infiltration on its own. We investigated whether subconjunctival injection of IL-4 can induce eosinophils to infiltrate into the conjunctiva. METHODS: Brown Norway rats were subconjunctivally injected with IL-4, eotaxin, or phosphate buffered saline (PBS), and the conjunctivas were harvested for histologic analysis (including immunohistochemistry) 6, 12, 18, and 24 hr later. The harvested conjunctivas were also subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to examine chemokine expression. In a separate experiment, the effect of coadministering interferon-gamma (IFN-gamma) along with IL-4 was examined. RESULTS: The subconjunctival injection of IL-4 induced eosinophil infiltration into the conjunctiva in a dose-dependent manner. IL-4 was as potent as eotaxin. The eosinophilic infiltration started 6 hr after the injection and persisted for up to 24 hr after the injection. Other infiltrating cell phenotypes were noted but were also observed in conjunctivas injected with PBS alone. RT-PCR analysis demonstrated that IL-4 injection did not upregulate chemokine RNA expression in the conjunctiva. Coinjection of IFN-gamma suppressed the infiltration of eosinophils into the conjunctiva induced by IL-4 injection. CONCLUSIONS: The subconjunctival injection of IL-4 specifically induces eosinophils to infiltrate into the conjunctiva. In addition, IFN-gamma in the conjunctiva can counteract this effect of IL-4.

Animals↗

PubMed2005

Tumor-infiltrating cells as a prognostic factor in Hodgkin's lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients.

The present study aimed to describe the general tissular composition of the immune infiltrate observed in Hodgkin's lymphoma (HL) and its possible relationship with clinical and survival prognostic factors. In this retrospective study of 267 HL patients, the relative proportions of infiltrating T lymphocytes (CD4+, CD8+), natural killer cells (CD 56+, CD 57+), cytotoxic cells (Granzyme B+, TIA-1+) and dendritic cells (CD 21+, S-100+) were quantified immunohistochemically with tissue microarray technology. Our results confirm the predominance of CD4 + T lymphocytes in the background of tumoral cells, in addition to a high number of cytotoxic lymphocytes (CD8, CD 57 and TIA-1). Patients with low numbers of infiltrating CD8, CD 56, CD 57+cells and high numbers of Granzyme B and TIA-1+cells presented a significantly unfavourable clinical course (presence of leukocytosis, B symptoms, advanced clinical stage (III/IV), non-responding patients). A reduced infiltration of CD4+T lymphocytes was related with the presence of Epstein - Barr virus. Significantly longer survival times were observed in patients with a high level of infiltrating CD 57, as well as a low level of Granzyme B and TIA-1+cells (log-rank test). When evaluated in a multivariate model, high levels of infiltrating TIA-1 and Granzyme B+cells were shown to be independent prognostic factors that negatively influenced overall survival. The presence of TIA-1+cells was found to be the only unfavorable prognostic factor of event-free survival and disease-free survival. The overall detection of tumor-infiltrating cells in HL confirms the importance of cytotoxic T lymphocyte infiltration (Granzyme B and TIA-1+cells) in these patients. Independently of the classical clinical and pathological features, these cells appear to be an unfavourable prognostic factor in HL and, more particularly, the presence of cytotoxic TIA-1+cells.

Adolescent↗

PubMed1986

Leukocytic infiltrates in idiopathic dilated cardiomyopathy. A source of confusion with active myocarditis.

The histologic criteria for the endomyocardial biopsy diagnosis of idiopathic dilated cardiomyopathy (IDCM) and active idiopathic/viral myocarditis are unclear. The present study was undertaken to characterize the nature of the inflammatory cell infiltrates in IDCM and thereby refine the differential diagnostic criteria for distinguishing IDCM from myocarditis using endomyocardial biopsy. We examined a mean of 6.2 large random sections from excised hearts of all cardiac transplant recipients at Stanford University with a diagnosis of IDCM, from June 1968 through June 1984. The 108 cases were evaluated for inflammatory cell type, extent, and location. Thirteen percent had no infiltrate, 32.5% had 1-5 foci of at least five inflammatory cells, 47% had 6-30 foci, and 7.5% had 30 or more foci. The infiltrates were primarily lymphocytic; while they were usually in the myocardial parenchyma, infiltrates were also located in zones of fibrosis, the endocardium, the epicardium, and surrounding vessels. Pretransplant biopsies in 56 of the 108 cases were available for review, and 55% of these contained inflammatory cell infiltrates. Agreement between the presence of infiltrates in the biopsy and the resected heart was obtained in 64%. This study highlights the high incidence of inflammatory cell infiltrates in the hearts of patients with IDCM. It reinforces the need for interpreting lymphocytic infiltrates in an endomyocardial biopsy with caution, as their mere presence does not necessarily imply a diagnosis of active myocarditis.

Adolescent↗

PubMed1995

Tumor biology of infiltrating lobular carcinoma. Implications for management.

OBJECTIVE: The purpose of this study was to characterize the biologic determinants that affect the behavior and management of infiltrating lobular cancer. METHODS: A prospectively accrued data base containing 1548 breast cancer cases was queried for specific pathologic and mammographic features. From this data base, 777 patients treated and followed-up at the H. Lee Moffitt Cancer Center were reviewed, and comparisons were made between the following three histologic subgroups: 661 infiltrating ductal (ID), 42 infiltrating ductal plus infiltrating lobular (ID + IL), and 74 infiltrating lobular (IL). RESULTS: Comparisons of the three histologic forms of breast cancer demonstrated the following: 1. At diagnosis tumors with IL components were larger than those with ID components (p < 0.001); in addition, a greater percentage of IL cancers were T3 lesions (14.8%), compared with ID cancers (4.5%). 2. Sizes of IL tumors were underestimated frequently by mammographic examinations when compared with pathologic measurements (p < 0.001). 3. By comparison to ID tumors, increasing IL tumor size is less likely to be associated with an increased number of metastatic lymph nodes per patient (p = 0.09). 4. Infiltrating lobular cancers treated by lumpectomy with cytologic surgical margin analysis more often gave false-negative results than did ID cancers (p < 0.001). 5. Infiltrating lobular cancers treated by lumpectomy required conversion to mastectomy over 2 times more frequently than ID cancers treated by lumpectomy. 6. Mastectomy was performed more frequently than lumpectomy for the treatment of IL versus ID tumors (p = 0.039). CONCLUSIONS: Infiltrating lobular cancers are biologically distinct from ID cancers. Although lumpectomy may be performed safely in selected patients, multiple difficulties exist in the management of IL cancer, particularly when breast conservation is chosen.

Adult↗

PubMed2000

Confluent choroidal infiltrates with sarcoidosis.

PURPOSE: To report the occurrence of confluent plaquelike choroidal infiltrates in four patients with sarcoidosis. METHODS: The medical records of patients with choroidal plaquelike infiltrates and presumed systemic sarcoidosis seen in the Mayo Clinic were reviewed. RESULTS: The cohort included four patients with confluent plaquelike choroidal infiltrates and systemic sarcoidosis. The most common ophthalmic symptom experienced by the patients was mild blurring of vision. The salient ophthalmic findings were choroidal infiltrates generally unaccompanied by other features frequently seen with sarcoidosis such as periphlebitis, multiple small yellowish choroidal infiltrations, vitreous cellular reaction, and granulomatous anterior uveitis. The choroidal lesions were confluent, yellowish, irregularly thickened infiltrates that frequently radiated peripherally from a peripapillary location in an ameboidlike pattern. Fluorescein angiography demonstrated early hypofluorescence and progressive patchy hyperfluorescence with late staining of the active lesions. Treatment with either systemic or subconjunctival steroids was associated with improvement in vision and partial resolution of the choroidal lesions. In two patients some of the lesions resolved spontaneously and became replaced by areas of chorioretinal atrophy. CONCLUSION: Plaquelike yellowish choroidal infiltrates associated with systemic sarcoidosis may occur in eyes remarkably free of other signs of inflammation. The infiltrates tend to radiate from the region of the optic nerve in a confluent ameboidlike pattern. They generally respond to corticosteroids and may be the first recognized manifestation of systemic sarcoidosis.

Adrenal Cortex Hormones↗

PubMed1987

Leukocyte subsets infiltrating into fully allogeneic, long-surviving rat liver allografts.

Leukocyte subsets that infiltrated into unmodified LEJ(RT1j)2 liver grafts from WKAH(RT1k) hosts were studied. This strain combination is fully allogeneic and yields acute rejections in skin and kidney transplantations. On days 3, 7, and 14, cellular infiltrates gradually increased, and many hepatocytes were degenerative and lost cellular glycogen. Blastoid lymphocytes were frequently seen, and mitotic features of hepatocytes were prominent (on day 14, 3 to 4/10 high-power fields). Later, on days 30, 50, and 300, the cellular infiltrates gradually subsided, and blastoid lymphocytes were rarely seen. Throughout the course, Ia+ cells (RT1.Dk+ and/or RT1.B+ cells) were the major cell populations infiltrating into the grafts. Most of the host RT1.D+ cells were histiocytoid in appearance on immunoelectron microscopy. Histiocytoid cells were the most numerous infiltrating cells, constituting 30-50% of the total infiltrating cells. There were different distributions of T cell subsets between the portal and sinusoidal areas, as we previously observed in acutely rejected rat renal allografts. Both RLyt-1+,2-(Th) and RLyt-1+,2+(Tc/s) cells were found almost equally in the portal area, while RLyt-1+,2+(Tc/s) cells predominated over RLyt-1+,2-(Th) cells in the sinusoidal area. However, a gradual replacement of RLyt-1+,2-(Th) cells by RLyt-1+,2+(Tc/s) cells, as seen in the perivascular area of renal grafts, was not found in the portal areas of the liver grafts. Except for the latter finding, the pattern of cellular infiltrates was similar to that of acute renal rejection, and the significance of these cellular infiltrates is discussed.

Animals↗

PubMedDate not supplied

Multislice computed tomography in planning nephron-sparing surgery in a prospective study with 76 patients: comparison of radiological and histopathological findings in the infiltration of renal structures.

OBJECTIVE: The aim of this prospective study is to determine the diagnostic accuracy of multidetector-row computed tomography (CT) compared to histopathologic findings in tumor staging of renal cell carcinoma, with the focus on tumor stage, vein and artery infiltration, and infiltration of the renal pelvis. MATERIALS AND METHODS: In a prospective study, a total of 76 consecutive patients with suspected renal cell carcinoma were preoperatively assessed for tumor staging using multidetector-row CT. Triphasic CT imaging (i.e., noncontrast, arterial, and parenchymal phase) was performed using multidetector-row CT with reconstructed slice thicknesses of 2 and 5 mm. Two blinded readers evaluated the CT scans independently; the results were then correlated with the histopathologic results. RESULTS: A total of 56 renal cell carcinomas were proven on histopathology. Readers 1 and 2 reached a sensitivity of 1.0 and 1.0 and a specificity of 0.41 and 0.42 for arterial infiltration, a sensitivity of 1.0 and 0.86 and a specificity of 0.58 and 0.5 for venous infiltration, and a sensitivity of 0.75 and 1.0 and a specificity of 0.5 and 0.44 for infiltration of the renal pelvis. The correlation between both readers was 0.7 for all modalities. CONCLUSIONS: The multiplanar reconstruction capability of multidetector-row CT allowed good sensitivity in predicting arterial infiltration. The lowest specificity was reached in excluding infiltration of the renal pelvis. Despite its high temporal and spatial resolution, the capacity of multidetector CT to predict intrarenal infiltrations is still limited.

Adult↗

PubMed2001

Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic approach using non-invasive and bronchoscopic procedures.

BACKGROUND: The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. METHODS: The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. RESULTS: An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29), Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%). The results obtained with the different techniques led to a change in antibiotic treatment in 93 cases (46%). Although changes in treatment did not have an impact on the overall mortality, patients with pulmonary infiltrates of an infectious aetiology in whom the change was made during the first 7 days had a better outcome (29% mortality) than those in whom treatment was changed later (71% mortality; p=0.001). CONCLUSIONS: Non-invasive and bronchoscopic procedures are useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic yield and impact on therapeutic decisions.

AIDS-Related Opportunistic Infections↗

PubMed2005

Imaging features of perivascular fatty infiltration of the liver: initial observations.

PURPOSE: To retrospectively identify and describe the imaging features that represent perivascular fatty infiltration of the liver. MATERIALS AND METHODS: The institutional review board approved the study and waived informed consent. The study complied with the Health Insurance Portability and Accountability Act. Ten patients (seven women, three men; mean age, 78 years; range, 31-78 years) with fatty infiltration surrounding hepatic veins and/or portal tracts were retrospectively identified by searching the abdominal imaging teaching file of an academic hospital. The patients' medical records were reviewed by one author. Computed tomographic (CT), magnetic resonance (MR), and ultrasonographic (US) imaging studies were reviewed by three radiologists in consensus. Fatty infiltration of the liver on CT images was defined as absolute attenuation less than 40 HU without mass effect and, if unenhanced images were available, as relative attenuation at least 10 HU less than that of the spleen; on gradient-echo MR images, it was defined as signal loss on opposed-phase images compared with in-phase images; and on US images, it was defined as hyperechogenicity of liver relative to kidney, ultrasound beam attenuation, and poor visualization of intrahepatic structures. Perivascular fatty infiltration of the liver was defined as a clear predisposition to fat accumulation around hepatic veins and/or portal tracts. For multiphase CT images, the contrast-to-noise ratio was calculated for comparison of spared liver with fatty liver in each imaging phase. RESULTS: Fatty infiltration surrounded hepatic veins in three, portal tracts in five, and both hepatic veins and portal tracts in two patients. Six of the 10 patients had alcoholic cirrhosis, two reported regular alcohol consumption (one of whom had acquired immunodeficiency syndrome and hepatitis B), one was positive for human immunodeficiency virus, and one had no risk factors for fatty infiltration of the liver. In three of the 10 patients, fatty infiltration was misdiagnosed as vascular or neoplastic disease on initial CT images but was correctly diagnosed on MR images. CONCLUSION: Perivascular fatty infiltration of the liver has imaging features that allow its recognition.

Adipose Tissue↗

PubMed1985

Focal lymphocytic infiltration in thyroids of elderly people. Histopathological and immunohistochemical studies.

Histopathological studies were made on the thyroid glands obtained from 169 autopsy cases of patients, ranging in age from 63 to 97 years, who had not had collagen diseases. Focal lymphocytic infiltration was found in 29 (17.2%) of 169 thyroid glands. Although the relationship between the incidence and age was unclear among elderly people, there was a tendency of a prevalence in females with respect to severity of focal lymphocytic infiltration. Immunohistochemically, a predominance of T cells (80-90%) was found in the thyroid lesions. The infiltrating T cells were composed of chiefly OKT 4+ or Leu 3a+ subset (60-80%) and lesser number of OKT 8+ or Leu 2a+ subset (20-40%). An increase in the percentage of OKT 8+ or Leu 2a+ cells, however, was observed in the tiny lesions infiltrating the interfollicular connective tissues. In aged patients over 63 years old, the average weight of thyroid glands without lymphocytic infiltration, obtained from female patients, was approximately 11 g, and the average weight of those with focal lymphocytic infiltration was approximately 17 g, whereas there was no significant difference in the weight of thyroid glands obtained from male patients with and without focal lymphocytic infiltration (14 g). The findings in the present study suggest that focal lymphocytic infiltration in thyroid glands is a focal sign of an immunological disorder which is based on autoimmunity associated with aging.

Aged↗

PubMed1990

Possible role for platelet-activating factor in neutrophil infiltration in allergic inflammation in rats.

Allergic inflammation was induced by injecting an antigen solution into an air pouch made on the dorsum of immunized rats with the antigen azobenzene-arsonate-conjugated acetyl bovine serum albumin. In this model, leukocyte infiltration into the pouch fluid was prominent 4-8 h after the antigen challenge. Most of the infiltrated leukocytes were neutrophils. Administration of the platelet-activating factor (PAF) antagonists such as CV-3988 and L-652,731 into the air pouch 15 min before and at the time of the antigen challenge failed to suppress leukocyte infiltration at 8 h. However, when the PAF antagonist was injected into an air pouch 4 h after the antigen challenge, neutrophil infiltration at 8 h was suppressed in a dose-dependent manner. Combined treatment with the 5-lipoxygenase inhibitor AA861 and the PAF antagonist did not potentiate the effect of the PAF antagonist, suggesting that participation of leukotriene B4 in neutrophil infiltration in this model is negligible. Eosinophil infiltration was very weak at 8 h, and the PAF antagonist showed no significant effect. At 8 h, the PAF level in the serum of the immunized rats was significantly higher than that of the nonimmunized rats. Intravenous administration of the PAF antagonist 15 min before the antigen challenge suppressed leukocyte infiltration more effectively than local administration into the pouch. These results indicate that PAF plays a significant role in neutrophil infiltration in allergic inflammation.

Animals↗

PubMed1992

Comparison of substance P-induced and compound 48/80-induced neutrophil infiltrations in mouse skin.

It has recently been shown that substance P induces neutrophil infiltration in the skin, which is mediated through mast cell degranulation. Since substance P activates both skin mast cells and vascular endothelial cells, we compared the potencies of substance P and a mast cell-degranulating agent, compound 48/80, which is inactive for vascular endothelial cells, in inducing neutrophil infiltration in mouse skin. We also examined the effect of the C-terminal peptide of substance P, SP6-11, which is active for vascular endothelial cells, on compound 48/80-induced neutrophil infiltration in the skin. Subcutaneous administrations of substance P (10(-7) to 10(-5) M; 0.1 ml) and compound 48/80 (0.5-50 micrograms/ml) induced neutrophil infiltrations and mast cell degranulations in mouse skin in a concentration-dependent fashion. Moreover, substance P induced more neutrophil infiltrations than compound 48/80 in terms of the magnitude of mast cell degranulations. SP6-11 (10(-6) to 10(-4) M) induced no significant neutrophil infiltration or mast cell degranulation, but increased the vascular permeability of endothelial cells in the skin. Furthermore, SP6-11 enhanced compound 48/80-induced neutrophil infiltration without any increase in mast cell degranulation. Our results indicate that, in addition to mast cell degranulation, the activation of vascular endothelial cells is involved in substance P-induced neutrophil infiltration in the skin.

Analysis of Variance↗

PubMed1994

T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.

BACKGROUND: In viral myocarditis, we previously reported that natural killer cells infiltrate the heart first, then activated T cells infiltrate second and play an important role in the pathogenesis of the myocardial damage. METHODS AND RESULTS: To elucidate the nature of T-cell infiltration, using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the expression of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart by polymerase chain reaction (PCR). The PCR-amplified products were confirmed by Southern blot hybridization with a C beta cDNA probe. In contrast to spleen lymphocytes, the repertoire of V beta gene transcripts in the heart was restricted. The infiltrating cells expressing V beta 10 were found in six of eight hearts of mice with acute myocarditis. The infiltrating cells expressing V beta 8 and V beta 13 were found in four of eight hearts with myocarditis, respectively. Immunoperoxidase staining of serial sections of the heart of myocarditis for TCR alpha beta chains and TCR V beta 10 confirmed that the dominant population of infiltrating T cells expressed V beta 10 gene products. CONCLUSIONS: The restricted usage of TCR genes by infiltrating T-cells may indicate that a specific antigen in heart with myocarditis is targeted. Our findings raise the possibility of immunotherapy with monoclonal antibodies specific for TCR V beta elements to prevent T-cell-mediated myocardial damage in viral myocarditis.

Acute Disease↗

PubMed1996

The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice.

IL-2 mediates the regression of certain malignancies, but clinical use is limited because of associated toxicities, including parenchymal lymphocytic infiltration with multiple organ failure. Secondarily induced cytokines are important mediators of IL-2 toxicity and IL-2-induced lymphocyte-endothelial adherence and trafficking. The recently discovered C-C chemokines, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1alpha, have also been implicated in lymphocytic migration. We hypothesized that IL-2 alters cytokine, C-C chemokine, and adhesion molecule expression in association with parenchymal lymphocytic infiltration. C57BL/6 mice were injected with 3x10(5) IU of IL-2 or 0.1 ml of 5% dextrose intraperitoneally every 8 h for 6 d, then killed. IL-2 induced massive lymphocytic infiltration in the liver and lung and moderate infiltration in the kidney in association with organ edema and dysfunction. Immunostaining showed increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in association with this organ-specific lymphocytic infiltration. Flow cytometry showed increased expression of the corresponding ligands (lymphocyte function-associated antigen-1 and very late antigen-4) on splenocytes. IL-2 increased TNF-alpha mRNA and protein expression in the liver. Organs infiltrated by lymphocytes had increased TNF-alpha mRNA, whereas RANTES mRNA was increased in all organs, regardless of lymphocytic infiltration. IL-2 toxicity involves organ-specific TNF-alpha and RANTES production with increased ICAM-1 and VCAM-1 expression as potential mechanisms facilitating lymphocytic infiltration and organ dysfunction.

Animals↗

PubMed1996

Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.

Besides a prominent mononuclear cell infiltration of the islets of Langerhans, nonobese diabetic (NOD) mice also show massive cellular infiltrates of the submandibular and lacrimal glands concomitant with histological signs of tissue damage. To obtain insights into the mechanisms operative during the initiation and progression of tissue damage, we followed by in situ hybridization the appearance of cells containing mRNA of the gene encoding the proinflammatory cytokine TNF-alpha in the cellular infiltrates. Cells expressing TNF-alpha are mainly located in infiltrates, are absent in nonaffected glands, and are preferentially found among CD4 T cells. Secretion of TNF-alpha by gland-infiltrating cells was confirmed by an ELISPOT procedure. Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided by the observed significant reduction in the extent of infiltration in nonobese diabetic mice transgenic for a soluble TNF receptor p55 fused to the Fc part of human IgG3. This protection from infiltration is paralleled by decreased expression of the adhesion molecules ICAM-1 and VCAM-1 in submandibular and lacrimal glands. These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.

Animals↗

PubMed1986

Cytolytic T lymphocytes with natural killer activity in thyroid infiltrate of patients with Hashimoto's thyroiditis: analysis at clonal level.

T Lymphocytes from thyroid infiltrates and peripheral blood (PB) of 3 patients with Hashimoto's thyroiditis (HT) were cloned using a microculture system previously shown to allow the clonal expansion of virtually all PB T lymphocytes from normal individuals. The phenotypic and functional features of a total number of 153 clones from thyroid infiltrates and 206 clones from PB were examined and compared with those of 272 clones derived from normal PB and spleens. The majority of clones derived from thyroid infiltrates of patients with HT had the cytotoxic/suppressor (T8+) phenotype, whereas the majority of clones from PB expressed the helper/inducer (T4+) phenotype. In addition, a consistent proportion (25%) of clones derived from PB of one patient had a phenotype (T3+T4-T8-) that was only occasionally found on clones obtained from PB or spleens of normal subjects. Most clones derived from both PB and thyroid infiltrates of the patients with HT had cytolytic activity, assessed by a lectin-dependent cytolytic assay against the murine P815 tumor cell line. The high frequency of cytotoxic T cells in thyroid infiltrates was related to the increased proportion of T8+ cells, whereas enhanced percentages of cytotoxic cell precursors with T4+ and T3+T4-T8- phenotypes primarily accounted for the high frequency of cytolytic T cells in the PB of the same patients. Many cytolytic T cell clones derived from thyroid infiltrates also had natural killer activity against human K562 and MOLT-4 target cells. These data provide the first functional analysis of T lymphocytes infiltrating the thyroid gland in patients with HT and suggest that the high proportions of cytolytic T cell precursors found in both thyroid infiltrates and PB of these patients may be of importance in determining the tissue damage in thyroid autoimmune disease.

Antibodies, Monoclonal↗

PubMed1985

Echographic findings and histological feature of the thyroid: a reverse relationship between the level of echo-amplitude and lymphocytic infiltration.

In 43 patients with Graves' disease, 5 patients with painless thyroiditis and 30 patients with Hashimoto-thyroiditis ultrasonographical observations and histological examinations by needle biopsy of the thyroid were carried out simultaneously. In all cases the level of echo-amplitude was well correlated with the rate of lymphocytic infiltrations and fibrosis. In cases which exhibited marked lymphocytic infiltrations in the thyroidal biopsy specimen, no apparent echoes or very low amplitude echoes were observed in the whole thyroid and in cases in which replacement with lymphocytic infiltration was observed in almost a half part of the thyroid, several sonolucent regions were observed in the thyroid and in cases in which lymphocytic infiltration or fibrosis was observed sporadically, low-amplitude and uniform echoes were observed in the whole or several regions of the thyroid. In cases with no lymphocytic infiltration in the histological specimen, diffuse high-amplitude and uniform echoes were observed throughout the whole lobe of the thyroid. In patients with painless thyroiditis, the amplitude of echo was low when the level of lymphocytic infiltration was high and the echo-amplitude showed a tendency to increase along with the decrease in the rate of lymphocytic infiltration. From these observations it is concluded that echo-amplitude is well correlated with lymphocytic infiltration and fibrosis in patients with Hashimoto-thyroiditis, Hashitoxicosis and painless thyroiditis.

Graves Disease↗

PubMed1998

Chronic obstructive uropathy in severe combined immunodeficient (SCID) mice: lymphocyte infiltration is not required for progressive tubulointerstitial injury.

Progressive renal injury in humans and experimental animal models is characterized by tubular atrophy, infiltration of mononuclear inflammatory cells, and interstitial fibrosis. Permanent unilateral ureter ligation represents a reproducible model for investigating mechanisms of progressive kidney injury, and in the rat is characterized by tubular epithelial cell proliferation followed by apoptosis and progressive infiltration of monocytes and lymphocytes. Nevertheless, whether monocytes or lymphocytes play a dominant role in causing tubulointerstitial damage remains to be elucidated. In the current study, a model of chronic obstructive uropathy in the mouse is established and the role of lymphocyte infiltration in the evolution of the tubule and interstitial alterations is investigated. Permanent ligation of the left ureter in wild-type (C3H/HeJ) mice resulted in progressive atrophy of tubules and interstitial fibrosis compared with the contralateral kidney over a 30-d period. Immunoperoxidase studies on frozen sections taken from kidneys at 0, 3, 10, 20, and 30 d after ureter ligation showed that the tubulointerstitial injury was accompanied by a marked and progressive increase in interstitial macrophages and T lymphocytes, with no appreciable increase in B lymphocytes. No increase in inflammatory cells was detected in contralateral kidneys over the same time frame. The significance of T lymphocyte infiltration was examined by comparing the degree of tubular atrophy and interstitial fibrosis and the nature and quantity of the inflammatory infiltrate in wild-type mice and C3HSMn.C-Scid/J (SCID) mice subjected to permanent left ureter ligation. SCID mice have genetic defects in immunoglobulin and T cell receptor gene rearrangements and are devoid of circulating mature B and T lymphocytes. Wild-type and SCID mice developed tubular atrophy and interstitial volume expansion in the ligated kidney to the same degree and at the same rate. SCID mice developed a prominent and marked monocyte/macrophage infiltrate in the ligated kidney, which was essentially equal to that in wild-type mice. In contrast, consistent with the known absence of mature lymphocytes in SCID mice, there was essentially no T lymphocyte infiltration into the ligated kidney of SCID mice. These results demonstrate the effective establishment of the model of maintained unilateral ureter ligation in mice, which is readily applicable to genetic mutant strains thus allowing for specific investigation of the role of individual components of the inflammatory response in progressive tubulointerstitial injury. These studies further demonstrate that lymphocyte infiltration is not required for progressive tubular atrophy and increased interstitial fibrosis after maintained unilateral ureter ligation.

Animals↗