Human CD8(+) TCR-alpha beta(+) and TCR-gamma delta(+) cells modulate autologous autoreactive neuroantigen-specific CD4(+) T-cells by different mechanisms

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. (C) 1997 Elsevier Science B.V.