STUDIES OF THE AUTOLOGOUS MIXED LYMPHOCYTE REACTION

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In this project we are studying the immunoregulatory potential of human T cells which are activated by self-MHC antigens present on B cells or macrophages (autoreactive T cells). In previous studies we established autoreactive T cell clones which are maintained in IL-2 enriched cultures by periodic stimulation with autologous non-T cells. One of these clones, termed MTC-4, was found to have dual immunoregulatory potential, providing help for resting B cells and suppression for pokeweed-mitogen (PWM)-activated B cells. In current studies we showed that MTC-4 helper function involves recognition of class II MHC antigens by the MTC-4 cells via its T3-associated T cell receptor. Further, we showed that the helper function is mediated by a BCGF-like factor which is distinct from IL-2 and which acts on both resting (small) and activated (large) B cells. Also incurrent studies we showed that MTC-4 T cell suppressor function is elicited when MTC-4 cells are co-cultured with non-T cells (B cells plus monocytes) that are pre-incubated with PWM for four hours, but not with non-T cells pre-incubated with PWM for 24 hours; this implies that induction of suppressor function depends on a transiently expressed MHC-associated surface molecule. In addition, we showed that pre-treatment of non-T cells with neuraminidase leads to non-T cells which do induce MTC-4 suppressor function. This suggests that the glycosylation status of non-T cells surface antigen determines whether non-T cells elicit helper or suppressor function from the autoreactive T cell population. Finally, we showed that the MTC-4 T cell suppressor function is MHC-specific in the effector phase in that only MHC matched cells are able to be suppressed. This indicates that MHC recognition is necessary in the effector cell-target cell interaction. In all, these studies establish that autoreactive T cells can be induced to provide either help or suppression depending on the type of B cell stimulus. This bifunctionality endows autoreactive cells with the potential for important homeostatic function.