PubMed Health⌕ Search

Biomedical subjects

F Spinozzi

Publications and source records attributed to F Spinozzi.

At least 55 records · Page 3Linked to original sources
PubMed1995

Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands protects CD4+ allergen-specific T-cell clones from programmed cell death.

An optimal stimulation of CD4+ cells in an immune response requires not only signals transduced via the TcR/CD3 complex, but also costimulatory signals delivered as a consequence of interactions between T-cell surface-associated costimulatory receptors and their counterparts on antigen-presenting cells (APC). The intercellular adhesion molecule-1 (ICAM-1, CD54) efficiently costimulates proliferation of resting, but not antigen-specific, T cells. In contrast, CD28 and CD2 support interleukin (IL)-2 synthesis and proliferation of antigen-specific T cells more efficiently than those of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. Cypress-specific T-cell clones (TCC) were generated from four allergic subjects during in vivo seasonal exposure to the allergen. Purified cypress extract was produced directly from fresh collected pollen and incubated with the patients' mononuclear cells. Repeated allergen stimulation was performed in T-cell cultures supplemented with purified extract and autologous APC. The limiting-dilution technique was then adopted to generate allergen-specific TCC, which were also characterized by their cytokine secretion pattern as Th0 (IL-4 plus interferon-gamma) or Th2 (IL-4). Costimulation-induced proliferation or apoptosis was measured by propidium iodide cytofluorometric assay. By cross-linking cypress-specific CD4+ and CD8+ T-cell clones with either anti-CD3 or anti-CD2, anti-CD28, and anti-CD54 monoclonal antibodies, we demonstrated that CD4+ clones (with Th0- or Th2-type cytokine production pattern) undergo programmed cell death only after anti-CD3 stimulation, whereas costimulation with either anti-CD54 or anti-CD28 protects target cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1995

Gamma delta T-cell subset distribution in human semen from fertile donors.

PROBLEM: Gamma delta T-cell subset distribution has not been fully investigated in normal human semen. METHODS: We therefore carried out experiments by using a direct immunofluorescence staining technique followed by two-color cytofluorimetric analysis on mononuclear cell (MC) suspensions from ejaculates of ten healthy, fertile volunteers. Autologous peripheral blood MC were simultaneously analyzed and the results used for statistical comparison. RESULTS: The proportion of normal human semen lymphocytes bearing the gamma delta T-cell receptor for antigen was greatly increased compared with autologous circulating counterparts. Interestingly, the rise was mainly due to an overexpansion of cells expressing V delta 1 gene-encoded determinants on their surface. This contrasts with the normal blood picture, where most gamma delta T cells express V delta 2 conformational epitopes. CONCLUSIONS: The numerical and phenotypical differences in semen gamma delta T lymphocytes provide further evidence of a defined migrating lymphocyte subset balance in anatomically and physiologically distinct areas of the body. Their functional role, in terms of both helper and suppressor-cytotoxic activities in the nonsterile proximal portions of the male genital tract, now needs to be explored in detail.

Adult↗
PubMed1995

Gamma delta T lymphocytes in mumps meningitis patients.

Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the proportion of lymphocytes which bore the gamma delta T-cell receptor for antigen was significantly higher in CSF than in autologous and heterologous blood samples. gamma delta T-cell values in CSF of MM patients were also significantly higher than those calculated in CSF specimens from nine children with non-inflammatory neurological disorders. Whether and how the expanded CSF gamma delta T-lymphocyte subset, either CD8+ or double-negative (CD4-/CD8-), contributes to the eradication of mumps virus infection from the central nervous system represents a central focus of our ongoing research.

Antigens, CD↗
PubMed1995

Peripheral blood gamma delta T cells in human listeriosis.

A phenotypical analysis carried out by direct immunofluorescence and two-colour cytofluorometry showed that the number of lymphocytes bearing the gamma delta T-cell receptor heterodimer was increased in the blood of eight children with Listeria monocytogenes infection, mainly due to an expansion of cells identified by monoclonal antibodies which recognize V delta 2 gene products. These findings are further evidence that gamma delta T cells are in some way involved in the immune response directed against human intracellular pathogens.

Female↗
PubMed1995

Long term treatment of rheumatoid arthritis with high doses of intravenous immunoglobulins: effects on disease activity and serum cytokines.

OBJECTIVE: To evaluate the effects of long term treatment of rheumatoid arthritis (RA) with high doses of intravenous immunoglobulins (IVIg). METHODS: Ten patients with active RA and prior unsuccessful treatment with at least one slow acting antirheumatic drug were treated with 400 mg/kg of IVIg for the first three days and then once a month for 12 months. Clinical evaluation and laboratory analysis were performed every month. Serum levels of tumour necrosis factor alpha (TNF alpha), soluble interleukin-2 receptor (sIL-2R), IL-1 alpha, IL-1 beta, IL-6 and interferon gamma (IFN gamma) were measured at baseline and at three monthly intervals for 15 months. RESULTS: Although laboratory parameters were not influenced by the treatment, a late but significant clinical improvement was observed after six months. Serial measurement of cytokines revealed a rapid and persistent decrease in serum TNF alpha and a late and significant reduction in sIL-2R concentrations. CONCLUSION: This study suggests that IVIg can ameliorate the symptoms and improve the functional capability of RA patients. This effect is associated with a partial modulation of serum concentrations of inflammatory cytokines and, more interestingly, with a late decrease in sIL-2R which correlated with the late reduction in disease activity.

Adult↗
PubMed1995

CD26 and CD31 surface antigen expression on human colostral T cells.

The expression levels of CD26 and CD31 surface antigens, two adhesion/activation molecules with helper and suppressor activities, respectively, were found to be significantly higher on human colostral T cells (CD3+) than in autologous peripheral blood samples. These findings provide further phenotypical evidence that immune system T lymphocytes are compartmentalized in the mammary gland late in pregnancy and during lactation. The question of whether these overexpanded T lymphocyte populations in breast milk modulate in situ, either by enhancing or suppressing, the cellular and/or humoral immune response of the suckling infant remains to be answered. Additional studies are, therefore, needed to explore this intriguing field concerning the immunology of the colostrum.

Antibodies, Monoclonal↗
PubMed1995

IL-4 is able to reverse the CD2-mediated negative apoptotic signal to CD4-CD8- alpha beta and/or gamma delta T lymphocytes.

Activation of immature thymocytes or transformed T lymphocytes via T-cell receptor (TCR)/CD3 signalling can induce programmed cell death (apoptosis). Recent data indicate that anti-CD3/TCR monoclonal antibodies (mAb) also trigger apoptosis in activated (but not resting) mature peripheral blood T lymphocytes. Here we report that triggering of resting CD4-CD8-TCR alpha beta+ and/or TCR gamma delta+ via the alternative CD2-dependent activation pathway is able to induce programmed cell death. A pair of mitogenic anti-CD2 mAb provoked a dramatic rise in [Ca2+]i that was almost entirely sustained by extracellular fluxes, and the inhibition of membrane [Ca2+/Mg2+] ATPase. The resulting endonuclease activation was able to induce DNA fragmentation, as revealed by propidium iodide staining and gel electrophoresis. Induction of apoptosis was prevented by the presence of interleukin-4 (IL-4) as well as by endonuclease inactivation with 100 microM ZnCl2, but enhanced by the contemporary block of protein kinase C. Thus it seems that in resting T lymphocytes the strong calcium signal delivered by the alternative CD2 activation pathway may act as a negative apoptotic signal in both alpha beta and gamma delta T cells with low (non-major histocompatibility complex restricted) antigenic affinity, so limiting the extension of polyclonal T-cell growth.

Antibodies, Monoclonal↗
PubMed1995

Local expansion of allergen-specific CD30+Th2-type gamma delta T cells in bronchial asthma.

BACKGROUND: T lymphocytes infiltrating airways during the allergic immune response play a fundamental role in recruiting other specialized cells, such as eosinophils, by secreting interleukin 5 (IL-5), and promoting local and systemic IgE synthesis by producing IL-4. Whether these presumed allergen-specific T cells are of mucosal or systemic origin is still a matter of conjecture. MATERIALS AND METHODS: Immunophenotype, IL-4 production, and in vitro proliferative response to specific or unrelated allergens were analyzed in the bronchoalveolar lavage (BAL) fluid lymphocyte suspensions obtained from untreated patients with allergic asthma. Healthy subjects and patients affected by pulmonary sarcoidosis, a granulomatous lung disease characterized by infiltrating Th1 CD4+ lymphocytes, served as controls. RESULTS: The proportions of gamma delta T lymphocytes, mostly CD4+ or CD4- (-)CD8-, was higher in asthmatic subjects than in controls (p < 0.05). Most BAL gamma delta CD4+ lymphocytes of asthmatic patients displayed the T cell receptor (TCR)-gamma delta V delta 1 chain. While CD30 antigen coexpression on the surface of BAL alpha beta(+) T lymphocytes was low (ranging from 5 to 12%), about half of pulmonary gamma delta T cells coexpressed it. These cells produced IL-4 and negligible amounts of interferon-gamma (IFN gamma), and proliferated in vitro in response to purified specific but not unrelated allergens. In contrast, control or sarcoidosis gamma delta T cells never displayed the CD30 surface molecule or produced significant quantities of IL-4. CONCLUSIONS: These findings not only confirm our previous hypothesis that the allergen-specific Th2-type lymphocytes found in the lungs of asthmatic patients are gamma delta T cells belonging to airway mucosal immunocytes, but also strongly support the notion that asthma is a local rather than a systemic disease.

Adult↗
PubMed1994

Activation of cord T lymphocytes. IV. Analysis of surface expression and functional role of 1F7 (CD26) molecule.

A role for CD26 surface antigen (Ag) in both CD3- and CD2-mediated T cell activation has been previously demonstrated. To analyze the functional role of CD26 in the CD3- and CD2-induced activation pathways of cord T cells, which represent the most reliable source of Ag-unprimed T cells, we employed a newly developed anti-CD26 monoclonal antibody, termed anti-1F7, anti-CD3 and anti-CD2 in activating T lymphocytes. The results showed that CD26 Ag is expressed on the surface of almost all resting cord T cells and that its fluorescence intensity is enhanced by activation. The binding of anti-1F7 induced a decrease in CD26 membrane expression, with no detectable effect on the surface expression of other cord T cell-related molecules. Moreover, the modulation of CD26 resulted in an increase in anti-CD3-mediated cord T cell activation through an enhancement in intracellular calcium levels, IL-2 receptor expression, and IL-2 synthesis, whereas it had no effect on cord T cell activation induced by anti-CD2 or anti-CD2 plus exogenous IL-2. The fact that the selective involvement of CD26 in the activation pathway triggered by anti-CD3, but not anti-CD2, could be reversed by prior stimulation of cord T cells with anti-CD3 suggests that this functional feature, which resembles that of mature thymocytes, may be linked to the Ag-unprimed cell phenotype of cord T lymphocytes.

Antibodies, Monoclonal↗
PubMed1994

Abnormal gastrointestinal motility in patients with celiac sprue.

No study to date has objectively investigated whether the motor behavior of the small bowel is abnormal in celiac sprue. The purpose of this study was to systematically address this topic by means of intraluminal pressure recordings in a series of such patients. Sixteen subjects (nine adults, seven children, age range 2-69 years) with celiac sprue were recruited and studied while untreated. Manometric examination was carried out for 6 hr during fasting and 3 hr after a meal. Adult celiac patients displayed a significantly (mean +/- SEM) greater frequency of migrating motor complexes in comparison to controls during fasting (4.44 +/- 1.6 vs 2.45 +/- 0.20, P < 0.01), whereas no differences were found in the pediatric group with respect to this variable. Fasting motor abnormalities, chiefly represented by discrete clustered contractions, giant jejunal contractions, and bursts of nonpropagated contractions, were discovered in a high percentage in both groups of celiac subjects (89% in adults and 44% in children, respectively). Similar abnormalities were observed in the postprandial period, especially in adults. In conclusion, patients with celiac sprue frequently display discrete gastrointestinal motor abnormalities, which though perhaps nonspecific may account for several symptoms complained of by such patients.

Adult↗
PubMed1994

The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells.

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20-30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy.

Antineoplastic Agents↗
PubMed1994

Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients.

The expression and the functional role of the CD26 (1F7) T cell surface molecule, an ectoenzyme which seems to represent a functional collagen receptor of T lymphocytes and to have a role in T cell activation, were analysed in both peripheral blood (PB) and synovial fluid (SF) T cell samples from patients with active and inactive rheumatoid arthritis (RA). Although patients with active disease displayed higher percentages of PB CD26+ CD4+ T cells than inactive RA and control subjects, CD26 antigen expression on RA SF T lymphocytes was low. The anti-1F7 binding to the T cell surface, that led to CD26 antigen modulation and enhancement of both IL-2 synthesis by, and 3H-TdR incorporation of, anti-CD3- or anti-CD2-triggered PB T cells in RA and control subjects, was unable to affect significantly both expression and functional activity of RA SF T lymphocytes. Since the 1F7 antigen spontaneously reappeared on the surface of unstimulated SF T cells after 2-5 days of culturing, the low 1F7 antigen expression of anti-1F7 in the SF T cell compartment may be the result of in vivo molecule modulation exerted by the natural ligand in the joint, with important implications for T cell activation and lymphokine synthesis.

Adolescent↗
PubMed1994

CD26 surface antigen expression on peripheral blood T lymphocytes from children with Down's syndrome (trisomy 21).

A phenotypical analysis carried out by two-colour flow cytometry showed that the proportion of circulating CD4+ T lymphocytes co-expressing the membrane-associated ectoenzyme dipeptidyl peptidase IV (CD26 antigen), a functional collagen receptor involved in T-cell triggering through its interaction with the CD45 protein tyrosine phosphatase, was significantly lower in 28 children with non-translocated trisomy 21 (Down's syndrome) (DS) than that calculated in the bloodstream of 27 age- and sex-matched healthy controls. Agonist anti-CD26 monoclonal antibodies (MoAbs), such as anti-1F7, not only modulate the surface expression of this molecule, but also enhance the proliferative activity of normal human T cells via the CD3- and CD2-mediated activation pathways. T-lymphocyte proliferation induced by antigen or polyclonal T-cell activators, including anti-CD3 or -CD2 MoAbs, is severely impaired in DS. Although the physiological ligand of CD26 surface structure is unknown, the fact that CD4+ T lymphocytes found in the blood of trisomic subjects are mostly CD26- (anti-1F7-) suggests that their faulty mitogenic response may be due to phenotypical and, perhaps, strictly correlated functional abnormalities.

Adolescent↗
PubMed1993

Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response.

As cord T cells, a model of antigen (Ag)-unprimed cell, display a functional defect when stimulated through the CD3 molecule, the role of lymphocyte function-associated antigen 1(LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pairs in cord CD3-triggered T-cell activation was analyzed using specific monoclonal antibodies (mAb) against each adhesion molecule. The addition of anti-CD11a, anti-CD18, or anti-CD2 to both adult and cord peripheral blood mononuclear cells (PBMC) cultures led to a decrease in CD3-induced proliferation. In contrast, CD3-stimulated cord, but not adult, PBMC proliferation was markedly enhanced when anti-CD54 or anti-CD58 were added. Despite the fact that ICAM-1 and LFA-3 molecules were virtually absent on cord resting T cells, mAb against these two molecules boosted both mitogenesis of and interleukin (IL)-2 production by purified cord T cells stimulated with plastic immobilized anti-CD3. Cord T-cell supernatant levels of interferon-gamma (IFN-gamma) were undetectable with CD3 stimulation, slightly raised with CD58/CD3 costimulation, but normal when T cells were preincubated with IL-2 for 24 hr before being costimulated with anti-CD3/CD58. Evidence that IL-2 and IFN-gamma play a pivotal role in fully activating cord T cells came from the demonstration that IL-2 and IFN-gamma are able to bypass the CD3-proliferative defect through differential up-regulation of the adhesion molecules. It would, therefore, seem that ICAM-1 and LFA-3 molecules are crucially implicated in the CD3-activation pathway of Ag-unprimed T cells.

Adult↗