Specific interactions between a human CD4+ clone and autologous CD4+ bifunctional immunoregulatory clones.

The cellular communications between a human CD4+ clone and autologous CD4+ clones induced with the first clone are described. The autoreactive clones proliferated after stimulation with the inducer clone, but not after stimulation with autologous clones expressing irrelevant specificities. The inducer clone markedly lost its ability to interact with the autoreactive clones after the modulation of its T-cell receptor. The proliferation of the autoreactive clones stimulated with the inducer clone was blocked by anti-DR monoclonal antibody. Collectively, these findings indicate that the autoreactive clones recognize idiotypic-like determinants on the receptor of the inducer clone in conjunction with DR antigen. The regulatory activity of the autoreactive clones was assayed by co-cultivation with their target inducer clone. The autoreactive clones were not committed to a single program, they could either suppress or enhance the proliferation of the target cells depending on the state of activation of the target cells. Activated target cells were suppressed whereas non-activated cells were enhanced. It is predicted that antagonistic cytokines released from the autoreactive clones exert differential effects on the target clone.