Blood groups in immunogenetics.
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Biomedical subjects
Publications and source records attributed to P Rubinstein.
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T-cell lines established from individuals infected with human T-cell leukaemia virus (HTLV) or generated by co-cultivation of normal human T cells with HTLV-infected T-cells, express class II (HLA-D/DR or Ia) antigens of the major histocompatibility complex (MHC) and interleukin-2 (IL-2) receptors. Because the expression of these markers characterizes the differentiation of immunologically activated T cells, we have now explored the possibility that HTLV- infected T cells might be primed to autologous or allogeneic Ia antigens expressed by the infecting cells. Our studies on the capacity of HTLV-infected T cells to display responses on mixed lymphocyte culture indicate that such T cells as well as single-cell clones derived from them, react non-discriminatively to all known allelic variants of human HLA-D/DR antigens, including those expressed by the responding cells. This reaction is inhibited by antibody to human Ia and is not triggered by Ia-negative T-leukaemia cells. The structure recognized seems to be a common epitope determinant of human Ia antigens, as (HTLV-infected) T cells primed in vitro to one HLA-D/DR specificity display amplified responses to all other HLA-D/DR antigens. We therefore believe that autostimulation by a self-Ia determinant may trigger the clonal expansion of HTLV-infected T cells and potentiate autoimmune processes.
T lymphocytes possessing helper function produce soluble factors that greatly augment B-cell proliferation and differentiation into antibody-secreting cells. In humans the subset of T lymphocytes bearing the T4 surface antigen comprises most of the cells that display helper activity and recognize class II antigens of the major histocompatibility complex (MHC), while the subset bearing the T8 antigen comprises T cells recognizing class I MHC antigens and exhibiting cytotoxic or suppressor function. Monoclonal antibodies to T4 or T8 greatly inhibit the cognitive and effector function of cells with the corresponding phenotype. This function/phenotype correlation is not absolute, however, for there are many examples of T8-positive clones that recognize MHC class II antigens and have helper activity, as well as of T4-positive clones with suppressor or cytotoxic function. Recently a family of cell-surface neoantigens, which might be relevant to T-cell function and which are present on activated but not on resting T lymphocytes, has been identified in mouse and humans using monoclonal antibodies. Some of these antibodies block the cytolytic activity of alloreactive T-cell clones, suggesting the possible involvement of such molecules in the activation of cytotoxic T-cell clones or in the lytic process itself. We now describe a similar late-differentiation antigen (LDA1) that is expressed by human T lymphocytes only following activation and is recognized by a monoclonal antibody that inhibits the antibody-inducing helper function of T lymphocytes.
An increased incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in patients with congenital rubella syndrome (CRS). Thus, studies of children with CRS would be of great importance in following the development of IDDM in a susceptible population. A total of 242 children with CRS, 30 of whom already have diabetes (mean age, 17.4 +/- 0.3 years) have been evaluated. In this latter group, the frequency of HLA DR3 is significantly increased and that of HLA DR2 significantly decreased. While pancreatic islet cell cytotoxic or surface antibodies (ICSA) are found in 20.2% of the total population of patients with CRS, they are present in 50%-80% of patients with glucose abnormalities. In all but five of the ICSA-positive patients, glucose abnormalities are currently present. In addition, glucose intolerance is found in greater than 50% of the DR3-positive nondiabetic patients with CRS evaluated to date. The data demonstrate that patients with CRS at risk for IDDM have the same genetic and immunologic features seen in classic IDDM, namely the presence of HLA DR3 and the absence of HLA DR2 and the high prevalence of ICSA before decompensation.
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A previous report suggested a relationship between particular phenotypes of group specific component (Gc), and susceptibility or resistance to HIV infection, whereas other recent investigations failed to corroborate this finding. The present study demonstrated that Gc allele frequencies in white homosexual men corresponded to those expected, regardless of HIV serology and related disease. Assignment of phenotype was not influenced by Gc complexing secondary to tissue damage, or the process of infection per se. However, Gc allele frequencies in black patients with AIDS were significantly different from those in black control subjects, suggesting that the previously observed results might be in part explicable on the basis of gene admixture in ethnically mixed populations.
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