ANERGIC T-CELLS EFFECT LINKED SUPPRESSION

Although the phenomenon of T cell-mediated suppression is well establi shed, particularly in experimental models of transplantation, the mech anisms involved in this form of immunoregulation remain controversial. We have recently demonstrated, using an in vitro system, that anergic T cells can act as suppressor cells by competing for the membrane of the antigen-presenting cell (APC) and for locally produced interleukin -2. In the experiments described here we have explored the ability of anergic T cells to effect linked suppression in antigen-specific and a llospecific responses. We observed that anergic antigen-specific CD4() T cells can inhibit T cells restricted by a different major histocom patibility complex (MHC) class II molecule provided that both restrict ion elements are expressed by the same APC. In addition, anergic allos pecific clones could also effect linked suppression since they could r egulate not only T cells specific for the same alloantigen but also re sponder T cells with direct allospecificity for a second allogeneic MH C molecule or with indirect, self MHC-restricted allospecificity for a processed MHC class I alloantigen. Furthermore, the regulatory effect of the anergic T cells was dependent on cell contact, was not depende nt upon irradiation, and was maintained during in vitro culture. These data demonstrate that linked suppression can be effected by anergic T cells in vitro. In the clinical context this raises the possibility t hat induction of tolerance to a single alloantigen could serve to regu late the immune response to an allograft carrying several MHC and mino r antigen differences.