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Human CD8+ TCR-alpha beta(+) and TCR-gamma delta(+) cells modulate autologous autoreactive neuroantigen-specific CD4+ T-cells by different mechanisms.
Correale J; Rojany M; Weiner LP; Department of Neurology, USC School of
March 30, 1998
J Neuroimmunol. 1997 Dec;80(1-2):47-64. Unique Identifier : AIDSLINE

To investigate the regulatory interactions among autologous T-cells during the course of multiple sclerosis (MS), proteolipid protein peptide-specific CD4+ T-cell clones (TCCs) were irradiated and used as immunogens to stimulate purified populations of autologous CD8+ TCR-alpha beta+ and TCR-gamma delta+ T-cells isolated from the peripheral blood of MS patients, patients with other non-inflammatory neurological diseases, and healthy blood donors. The resulting blasts were expanded in the presence of hIL-2 and then cloned by limiting dilution. Two different groups of CD8+ TCCs were revealed. A first group of CD8+ TCCs recognized autologous CD4+ T-cells based in their TCRV beta structures (anti-idiotypic responsiveness). A second group of CD8+ TCCs recognized Ag activated autologous CD4+ TCCs irrespective of their Ag specificity or TCRV beta expression anti-ergotypic responsiveness). Both groups showed MHC class I restricted cytotoxicity against CD4+ T-cells and were able to secrete IFN-gamma, TNF alpha/beta and TGF-beta. TCR-gamma delta+ TCCs isolated in response to stimulation with autologous peptide-specific CD4+ TCCs showed only anti-ergotypic cytotoxicity, which was not inhibited by anti-MHC class Ia monoclonal antibodies. Moreover, they were able to secrete IFN-gamma and TNF alpha/beta, but not TGF-beta. These data demonstrate that regulatory mechanisms among human autologous T-cells can be mediated by cytolytic interactions or by the release of specific cytokines. Furthermore, they provide evidence that CD8+ TCR-alpha beta+ and TCR-gamma delta+ cells differ in their patterns of recognition and in their abilities to modulate the immune response mediated by autologous autoreactive CD4+ T-cells.

*Autoantigens/IMMUNOLOGY *CD4-Positive T-Lymphocytes/IMMUNOLOGY *CD8-Positive T-Lymphocytes/IMMUNOLOGY *CD8-Positive T-Lymphocytes/METABOLISM *Epitopes/IMMUNOLOGY *Receptors, Antigen, T-Cell, alpha-beta/IMMUNOLOGY *Receptors, Antigen, T-Cell, gamma-delta/IMMUNOLOGY