Antigen‐induced feedback suppression: antigen‐specific initiator T cells fail to recruit new antigen‐reactive cells in immunized mice

Experiments were carried out to investigate the control exerted by memory cells on the activation of virgin antigen‐reactive T cells. Spleen cells from normal mice, educated on human gamma‐globulin (HGG)‐fed macrophages, then injected into the footpads of syngeneic recipients, recruited antigen‐specific reactive lymphocytes in normal mice, but failed to do so in HGG‐tolerant or HGG‐immunized recipients. This inhibition of recruitment was antigen‐specific, since keyhole limpet hemocyanin (KLH) initiator lymphocytes did recruit KLH‐reactive cells in HGG‐immunized recipients. Spleen cells from immunized animals, unlike those from tolerant ones, were capable of supporting the generation in culture of HGG‐initiator lymphocytes. Hence, the suppression we observed in immunized mice cannot be simply attributed to conventional Ly 23 suppressor T cells. To analyze the mechanism of the observed suppression, we tested the capacity of initiator cells educated on macrophages fed simultaneously with KLH and HGG to recruit antigen‐reactive lymphocytes in normal as compared to immunized recipients. Such initiator lymphocytes recruited, in normal animals, both and HGG‐ and anti KLH‐reactive cells. Yet, in HGG‐immunized mice, initiator cells educated under similar conditions failed to recruit not only anti HGG‐reactive cells but also anti KLH‐reactive lymphocytes. This suggested that in HGG‐immunized recipients, stimulated by HGG initiators (or by HGG antigen), HGG memory cells may lead to the generation of a factor (or factors) which may then nonspecifically suppress the recruitment and maturation of virgin antigen‐reactive cells to unrelated antigens. This assumption is further strengthened by our findings which revealed that in the presence of HGG, spleen cells originating in HGG‐immunized mice exert a weaker mixed lymphocyte culture reaction to alloantigens. Thus, it appears that an antigen may induce, in the presence of specific activated memory cells, the generation of factors which may suppress antigen‐induced proliferation of certain T cell subsets. These results may contribute to our understanding of the possible homeostatic role played by memory T cells in feedback regulatory circuits existing among T cell subsets during immune processes. The possible role of such mechanisms in high‐ and low‐zone tolerance is discussed.