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The mechanisms by which glucocorticoids suppress immune responses have not yet been clearly defined. In steroid-sensitive pathological conditions, an increase in γδ T cells can occur in certain untreated systemic autoimmune disorders and seems to be a persistent feature in most cases of systemic lupus erythematosus (SLE). Our previously published data demonstrated that immunosuppressive therapy normalized this expanded SLE T cell subset in parallel with clinical remission of the symptoms. To establish how corticosteroid treatment determines the disappearance of peripheral blood γδ T lymphocytes, circulating αβ and γδ T lymphocytes from seven SLE subjects with active disease and seven healthy individuals were cultured in the presence or absence of 10-7 M Dexamethasone (DEX). Cell suspensions were then analysed for DNA fragmentation, characteristic of apoptotic cell death, by a new cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T cell populations was carried out for comparison. Regular follow-ups for 6 months revealed in vivo steroid treatment determined a dramatic fall in SLE blood γδ T cells, and in vitro experiments seem to indicate that DEX-triggered apoptotic signals are confined to the double negative (CD4-CD8-) γδ T cell subpopulation which disappears after in vivo immunosuppressive therapy. Clinical and pathological remission of some autoimmune diseases is often obtained by corticosteroids. Our results offer new insights on the mechanisms through these hormones exert their potent inhibitory activities on immune system cells postulated to play a role in the generation of autoimmune responses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Subjects with Down's syndrome (DS), or trisomy 21, have an increased susceptibility to infections, malignant diseases and autoimmune phenomena. Various arms of the immune system are severely impaired in trisomic patients. We found that the proportion of blood lymphocytes bearing the γ/δ T-ceIl receptor (TCR) was significantly higher in adults with trisomy 21 than in age- and sex-matched healthy controls. Interestingly, the increase was mainly due to an over-expansion of cells which bear non-covalently bound γ/δ chains on their surface. This contrasts with the normal blood picture, where the great majority of γ/δ T cells express the disulphide-linked form of the TCR. The fact that trisomic γ/δ T cells are both numerically and phenotypically unbalanced provides further evidence that immunological abnormalities are integral features of DS. [ABSTRACT FROM AUTHOR]

The proliferative response of purified T cells to anti-CD2 monoclonal antibodies (T 112 plus T 113) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+ /phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mcdiated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events. [ABSTRACT FROM AUTHOR]

Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T1I2; plus T1I3) monoclonal antibodies, Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study. Under certain experimental conditions (anti-CD3 or anti-CD2 antibody stimulation), the patients' lymphocytes expressed low levels of IL-2 surface receptors and failed to produce normal amounts of this lymphokine. Studies are currently in progress in our laboratories to determine whether these defects are due to an impairment of the early signalling events surrounding the complexing of CD3, CD2, or lectin receptors to their respective ligands. [ABSTRACT FROM AUTHOR]

Although the relative and absolute numbers of CD3+ cells (T lymphocytes) were similar in eight children with acquired Toxoplasma gondii infection and 10 uninfected age- and sex-matched healthy controls, the proportion of cells bearing the γδ T-cell receptor was significantly higher in the subjects with acute toxoplasmosis. The great majority of γδ T cells from the infected patients expressed covalently bound γδ chains on their surface, i.e. were BB3+ lymphocytes. Since the γδ T-cell subsets exert both restricted and unrestricted major histocompatibility complex cytotoxicity, further research is needed to elucidate the role of γδ T cells in the control of this coccidian protozoan infection. [ABSTRACT FROM AUTHOR]

Our laboratories previously reported that the proportion of lymphocytes bearing the γ/δ T-cell receptor (TcR) is twofold greater in human milk lymphocyte suspensions than in autologous and heterologous blood samples. The present investigation shows that γ/δ colostral T cells preferentially express non-covalently bound γ/δ chains, whereas only a few display the disulphide-linked form of the TcR. This contrasts with the picture in the blood, where the distribution of these two non-overlapping subpopulations is proportionally inverse. These findings are further evidence that the colonization of the mammary gland during lactanon by immune system cells is the result of a selective homing process. [ABSTRACT FROM AUTHOR]

The biological role of T cell receptor (TCR) gamma delta bearing cells is not yet fully understood. We studied 12 children with Bordetella pertussis infection and 12 age- and sex-matched healthy controls. Patients with whooping-cough yielded significantly lower relative and absolute numbers of blood TCR-gamma delta + cells than normal controls (both p < 0.001). It is suggested that the depletion of circulating gamma delta T cells in patients with Bordetella pertussis infection might be the result of the dispatch of these cells to the site of inflammation, i.e. the bronchial mucosa. Interestingly, other human lung diseases, such as allergic bronchial asthma and sarcoidosis display similar pulmonary phenotypical features.

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.

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.

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.