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At least 19 recordsLinked to original sources

Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases.

Human immunodeficiency virus (HIV) proteins were detected by immunohistochemistry in the duodenal and rectal mucosa of 30% of 127 AIDS patients studied. HIV-infected cells were present in the lamina propria in 95% of the positive biopsies. They were immune cells, either isolated lymphocytes and macrophages (1-4 per positive biopsy) or dendritic reticulum cells forming a network in the germinal centres of mucosal lymphoid follicles. HIV proteins were not found in the duodenal epithelium or in the superficial rectal epithelium. In two cases (5% of the positive biopsies), they were found in rectal glands: the HIV-infected cells could be either epithelial cells or immune cells. This study confirms that the gut can be a target organ for HIV and that HIV is mainly carried by gut immune cells. The phenotypic study of lymphoid populations and macrophages in the gut mucosa of AIDS patients showed an inverse CD4/CD8 ratio in the lamina propria, compared with normal controls. This was independent of the presence of HIV proteins and is probably responsible for the appearance of opportunistic infections in the mucosa. An increase in activated macrophages was also noted in the mucosa of AIDS patients.

Acquired Immunodeficiency Syndrome↗

In vitro senescence of immune cells.

Immune cells are eminently suitable model systems in which to address the possible role of replicative senescence during in vivo aging. Since there are more than 10(8) unique antigen specificities present within the total T lymphocyte population of each individual, the immune response to any single antigen requires massive clonal expansion of the small proportion of T cells whose receptors recognize that antigen. The Hayflick Limit may, therefore, constitute a barrier to effective immune function, at least for those T cells that encounter their specific antigen more than once over the life course. Application of the fibroblast replicative senescence model to the so-called cytotoxic or CD8 T cell, the class of T cells that controls viral infection and cancer, has revealed certain features in common with other cell types as well as several characteristics that are unique to T cells. One senescence-associated change that is T cell-specific is the complete loss of expression of the activation signaling surface molecule, CD28, an alteration that enabled the documentation of high proportions of senescent T cells in vivo. The T cell model has also provided the unique opportunity to analyze telomere dynamics in a cell type that has the ability to upregulate telomerase yet nevertheless undergoes senescence. The intimate involvement of the immune system in the control of pathogens and cancer as well as in modulation of bone homeostasis suggests that more extensive analysis of the full range of characteristics of senescent T cells may help elucidate a broad spectrum of age-associated physiological changes.

Aging↗

Interfaces between dendritic cells, other immune cells, and nerve fibres in mouse Peyer's patches: potential sites for neuroinvasion in prion diseases.

In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to dendritic cells, viewed as candidate transporters of infectious prion. Double immunofluorescence labellings with anti-CD11c antibody and marker for other immune cells (B cells, T cells, follicular dendritic cells) were carried out and analysed by confocal microscopy on Peyer's patch cryosections. To reveal the extensive ganglionated networks of the myenteric and submucosal plexi and the sparse meshworks of nerve strands, we used antibodies directed against different neurofilament subunits or against glial fibrillary acidic protein. In the suprafollicular dome, dendritic cells connect, via their cytoplasmic extensions, enterocytes with M cells of the follicle-associated epithelium. They are also close to B and T cells. Nerve fibres are detected in the suprafollicular dome, notably in contact with dendritic cells. Similar connections between dendritic cells, T cells, and nerve fibres are seen in the interfollicular region. Germinal centres are not innervated; inside them dendritic cells establish contacts with follicular dendritic cells and with B cells. After immunolabelling of normal prion protein, dendritic cells of the suprafollicular dome are intensely positive labelled.

Animals↗

Cutaneous basophil-associated resistance to ectoparasites (ticks). I. Transfer with immune serum or immune cells.

Immune resistance experiments were carried out in guinea-pigs employing two tick species that as adults are ectoparasites of cattle (Ixodes holocyclus and Rhipicephalus appendiculatus). These studies showed that susceptibility of non-immune guinea-pigs to infestation with tick larvae varies according to the species of tick and the strain of guinea-pig. With both tick species, greater than 90% acquired resistance was achieved in several guinea-pig strains. Immune resistance was evident within a week following primary infestation and lasted up to 9 months following a single sensitizing exposure to tick feeding. The strength and duration of resistance was influenced strongly by the size of the initial sensitizing dose. Immune resistance was readily transferred to naive recipients by intravenous administration of either peritoneal exudate cells or immune serum from donors sensitized by a single prior infestation with ticks. Doses of serum as small as 0.5 ml transferred resistance. These studies demonstrate that both sensitized cells and immune serum factors contribute significantly to acquired host resistance to ticks that as adults are ectoparasites of cattle.

Animals↗

Fas (Apo-1/CD95) and Fas ligand interaction between gastric cancer cells and immune cells.

BACKGROUND AND AIMS: It has been proposed that the expression of Fas ligand (Fas L) in tumors may play an important role in immune escape. This study was undertaken to test a 'counterattack' theory as a mechanism of immune escape in gastric carcinoma. METHODS: Expression of Fas and Fas L was examined in the human gastric cancer cell lines using reverse transcription-polymerase chain reaction. Cytotoxicity was determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Apoptosis of target Jurkat cells was examined after coculture with the effector gastric cancer cells in vitro. Immunohistochemical staining was performed for the detection of Fas and FasL in tumor-infiltrating lymphocytes (TIL) and gastric cancer cells in vivo. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method in vitro and in vivo. RESULTS: Fas and FasL mRNA were found to be differentially expressed in gastric cancer cell lines. The coculture experiment showed that apoptosis of Jurkat was induced by a FasL-overexpressing effector gastric cell SNU-484. In a Fas-expressing gastric cell SNU-638, Fas expression was upregulated by the treatment of gamma-interferon in a time- and concentration-dependent manner. SNU-638 treated with gamma-interferon was more sensitive to anti-Fas antibody-mediated cytotoxicity than was the control cell line, suggesting an increase of functional Fas in gastric cancer cells. The expression of FasL in gastric cancer cells and of Fas in apoptotic TIL was also detected in vivo. CONCLUSION: The data indicate that the FasL expression of gastric cancer cells supports a 'counterattack theory' in gastric cancer cells and that the upregulation of Fas by IFN-gamma in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells. This result is supported by the expression of FasL in gastric cancer cells and apoptotic TIL in vivo. It is implicated that the different biological behaviors of gastric cancer cells could be at least in part explained by Fas and FasL interaction with immune cells.

Apoptosis↗

[Plasmacytoid monocytes and plasmacytoid dendritic cells. Immune system cells linking innate and acquired immunity].

Plasmacytoid monocytes (PM), originally described by pathologists as cells occurring in the interfollicular area of human lymph nodes, are emerging cells in the scenario of the immune system. PM normally circulate between peripheral blood, lymphoid organs and sites of inflammation using specific migratory pathways and signalling; PM are easily recognizable on the basis of their distinctive morphology and phenotype (CD3-, CD11c-, CD14-, CD20-, CD36+, CD56-, CD68+, CD123+, BD-CA2+). Recently it has been shown that PM produce high levels of type I interferon, thus corresponding to natural interferon-producing cells. Furthermore, PM or their precursors may differentiate in vitro towards a new subset of dendritic cells, supporting a function in antigen-dependent T cell priming. Taken together, these data suggest PM play a relevant role in the immune system, linking innate and acquired immunities. In fact, PM seem to be crucial in the pathogenesis of different immune-mediated human diseases including viral infections and autoimmune disorders, and to be involved in the immune control of some malignant neoplasms. The issue concerning the cell lineage of PM remains unresolved, but the frequent association between a tumoral expansion of PM and myelo-monocytic leukemia, together with cytogenetic identity between the two cell populations identified in rare cases, corroborates the myeloid origin of PM.

Animals↗

Treatment of disseminated leukemia with cyclophosphamide and immune cells: tumor immunity reflects long-term persistence of tumor-specific donor T cells.

B6 mice bearing disseminated syngeneic FBL leukemia can be cured by treatment on day 5 with 180 mg/kg cyclophosphamide and 2 x 10(7) adoptively transferred syngeneic immune spleen cells. Complete tumor eradication in this model requires more than 30 days and is dependent upon the transfer of specifically immune T cells. To evaluate the relative contributions of host and donor T cells to tumor elimination and the maintenance of tumor immunity, donor cells obtained from Thy congenic mice were used for adoptive transfer. Thus, host and donor T cells could be readily distinguished by the expression of either Thy-1.2 or Thy-1.1 antigen. The results demonstrated that the majority of immunologically competent T cells present in hosts cured by adoptive therapy were of host origin. A small population of donor T cells, however, persisted long after transfer. At day 60, a time point shortly after tumor eradication had been completed, 5% of splenic T cells were of donor origin, and by day 120 this percentage had decreased to less than 2%. Functional studies performed at both time points revealed that this small number of residual donor T cells contained the subpopulation of tumor-reactive T cells present in the host. Thus, host T cells did not make a substantial contribution to the expression of the anti-tumor response and presumably have little role in either tumor eradication or the long-term maintenance of tumor immunity.

Animals↗

Deficient cell-mediated immunity in head and neck cancer patients secondary to autologous suppressive immune cells.

Fifty-four patients with epidermoid head and neck cancer were studied with routine and modified mixed leukocyte culture (MLC) techniques to quantify and characterize their cell-mediated immunity (CMI). Of these, 67% demonstrated deficient CMI in MLC. Employing G-10 column filtration to remove adherent cells selectively, the authors found that 56% of these deficient individuals demonstrated significantly increased lymphocyte responsiveness in MLC. Returning the adherent cells to the cultures usually recaptured the suppressive effect of these adherent cells. Cell marker analyses reveal that the macrophage is the most likely candidate for this suppressive cell. Therapeutic measures which address this paradoxically suppressive cell could be of benefit in enhancing CMI and gaining tumor control.

Carcinoma, Squamous Cell↗

Differences in immune cells engaged in cell-mediated immunity after chemotherapy for far advanced pancreatic cancer.

OBJECTIVES: Little is known about the effects of chemotherapy on the immunity of cancer patient or the ideal timing for immunotherapy combined with chemotherapy. To address these questions, we evaluated the effect of gemcitabine and cisplatin combination chemotherapy on the immunity of pancreatic cancer patients. METHODS: Thirteen patients with far advanced pancreatic cancer were enrolled and 7 sex- and age-matched healthy volunteers were included as a control group. RESULTS: Compared with healthy controls, the amounts of peripheral blood mononuclear cells, dendritic cells (DCs), natural killer cells, CD4, and CD8 T cells were reduced. With this numerical suppression, NK cell cytotoxicity to K562 leukemia cells was also significantly impaired (7.7% +/- 4.9% versus 21.7% +/- 7.9% of DNA loss; P = 0.016). Serum concentrations of VEGF and interleukin-10 (IL-10) were higher than the control group (192.1 +/- 114.7 versus 50.8 +/- 39.5 pg/mL of vascular endothelial growth factor (VEGF) and 122 +/- 68.9 versus 111.4 +/- 37.4 pg/mL of IL-10). After 1 cycle of gemcitabine and cisplatin chemotherapy, the impaired immunity of patients with pancreatic cancer was restored. Specifically, the recovery of DCs occurred rapidly and exceeded the value of healthy controls. Levels of the immunosuppressive cytokines, IL-10 and VEGF, gradually decreased during chemotherapy. CONCLUSIONS: Systemic chemotherapy seems to be beneficial for restoring the impaired immunity of patients with pancreatic cancer, and one of the ideal times to collect DCs for immunotherapy is after completing each cycle of chemotherapy.

Aged↗

Modulatory effects of several herbal extracts on avian peripheral blood cell immune responses.

Standardized ethanol extracts of Allium sativum (garlic), Glycyrrhiza glabra (licorice), Plantago major (plantain) and Hippophae rhamnoides (sea buckthorn) were assessed for their effects on cellular immunity in laying hens. Birds (n = 25) had blood samples taken and both specific and non-specific immune cell responsiveness were evaluated by a leukocyte proliferation assay, carbon clearance test and SRBC phagocytosis in monocyte-derived macrophage cultures. Licorice and sea buckthorn (50 microg/mL) clearly enhanced the macrophage membrane function (p < 0.05 and p < 0.01, respectively). Dual effects on circulating phagocytes were revealed for plantain and sea buckthorn, while garlic at 200 microg/mL impaired the phagocytic capacity of blood cells. None of the tested extracts showed mitogenic properties, but high concentrations of sea buckthorn (400 microg/mL) inhibited leukocyte proliferation. Small concentrations (20 microg/mL) of licorice proved the co-mitogenic potential for both T and B avian lymphocytes (p < 0.05). Certain extracts definitely enhanced the fowl innate and/or specific cell immunity and may therefore improve host resistance in poultry. Considering the chicken as an important non-mammalian model that also serves as an available laboratory approach for some human diseases, herbs exerting immunomodulatory properties may find relevant clinical applications.

Animals↗

CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity.

NKT cells are known to regulate effector T cell immunity during tolerance, autoimmunity, and antitumor immunity. Whether age-related changes in NKT cell number or function occur remains unclear. Here, we investigated whether young vs aged (3 vs 22 mo old) mice had different numbers of CD1d-restricted NKT cells and whether activation of NKT cells by CD1d in vivo contributed to age-related suppression of T cell immunity. Flow cytometric analyses of spleen and LN cells revealed a 2- to 3-fold increase in the number of CD1d tetramer-positive NKT cells in aged mice. To determine whether NKT cells from aged mice differentially regulated T cell immunity, we first examined whether depletion of NK/NKT cells affected the proliferative capacity of splenic T cells. Compared with those from young mice, intact T cell preparations from aged mice had impaired proliferative responses whereas NK/NKT-depleted preparations did not. To examine the specific contribution of NKT cells to age-related T cell dysfunction, Ag-specific delayed-type hypersensitivity and T cell proliferation were examined in young vs aged mice given anti-CD1d mAb systemically. Compared with young mice, aged mice given control IgG exhibited impaired Ag-specific delayed-type hypersensitivity and T cell proliferation, which could be significantly prevented by systemic anti-CD1d mAb treatment. The age-related impairments in T cell immunity correlated with an increase in the production of the immunosuppressive cytokine IL-10 by splenocytes that was likewise prevented by anti-CD1d mAb treatment. Together, our results suggest that CD1d activation of NKT cells contributes to suppression of effector T cell immunity in aged mice.

Aging↗

Interactions between epithelial cells and immune cells in the intestine.

Not merely a passive barrier as previously assumed, epithelial cells act as sensitive indicators of infection that initiate defense responses. Noninvasive as well as invasive organisms have been demonstrated to elicit production of chemoattractants. That noninvasive organisms have this capacity suggests that receptor-mediated signaling pathways may be involved. Epithelial cells have been found to release both chemokines and cytokines in a precise mixture that varies according to the origin or maturity of the cell. Different microorganisms also elicit different response patterns. The information presented provides a basis for a new view of epithelial cell function in relation to host defense.

Animals↗

Circulating immune cells and immune complexes in peripheral blood of healthy and of bovine leukemia virus-infected cows and lymphosarcomatous calves.

The peripheral blood (lymphocytes and immune complexes (IC) from 20 healthy cows, 5 healthy calves, 10 bovine leukemia virus-infected cows and 4 lymphosarcomatous calves was investigated using 4 different immunological techniques. A highly significant increase in the percentage of surface immunoglobulin (SIg)-bearing peripheral blood lymphocytes of persistent lymphocytosis-cows could be demonstrated while the percentage was decreased in the lymphosarcomatous calves. Percentages of spontaneous sheep red blood cells(SRBC)-rosettes (E-rosettes) were not elevated. Antibodies to bovine leukemia virus-antigen were detected in the sera (immuno-diffusion test) of all the leukotic cows but not of the lymphosarcomatous calves. Although there seems to be an increased level of IC in the advanced stage, as compared to the beginning of the disease, there was no statistically significant difference in comparison with the control individuals. In the lymphosarcomatous calves as well as in the leukemic cows there was no statistical difference in the IC values between diseased animals and controls.

Animals↗

Cell-cell interactions in synovitis. Endothelial cells and immune cell migration.

Leukocyte ingress into the synovium is a key process in the pathogenesis of rheumatoid arthritis and other inflammatory conditions. In this review, the role of endothelial cells in leukocyte extravasation will be discussed, including the role of the most relevant cellular adhesion molecules. These molecules play an important role in mediating leukocyte--endothelial interactions. It is likely that different adhesive pathways are involved in different steps of leukocyte adhesion to and migration through endothelia. Targeting of pathological endothelial function, including leukocyte--endothelial adhesion, may be useful for the future management of inflammatory arthritis.

Animals↗