The regulation of antibody secreting cells generated in the autologous mixed leukocyte reaction in man.

Although the autologous mixed leukocyte reaction (AMLR) is usually defined as a proliferative response of T cells to autologous non-T cells, the reaction also results in the synthesis of immunoglobulin (Ig) by B cells. The induction of Ig synthesis has an absolute requirement for helper (Leu 3+) T cells, whereas suppressor (Leu 2+) cells inhibit the response. To assess the immunoregulatory potential of T cells activated in this reaction, 8 day cultures between T and autologous non-T cells were carried out, after which the activated T cells were fractionated into subsets with monoclonal antibodies to T cell markers and HLA-DR antigen. Each population was cocultured in fresh AMLR, and on the 8th day of culture, Ig secreting cells were measured in a reverse hemolytic plaque assay. The results show that activated Leu 2+ DR+ T cells were at least 50 times more potent as suppressors of IgM and IgG synthesis than fresh Leu 2+ cells alone. The activation of this Leu 2+ DR+ subpopulation required Leu 3+ cells in the primary culture. Furthermore, in the absence of fresh Leu 2+ cells in the second culture, little or no suppression was observed, suggesting that the Leu 2+ DR+ cells act to amplify or induce suppressor effects of fresh Leu 2+ cells. The possibility that suppressor-amplifier and suppressor-effector cells are derived from phenotypically distinct resting cells was supported by additional experiments utilizing a monoclonal antibody (anti-Leu 8) that subdivides resting Leu 2 cells. Thus, neither Leu 2+ 8+ nor Leu 2+ 8- cells alone suppress Leu 3+ induced immunoglobulin synthesis, but in combination the subsets are markedly inhibitory. These results indicate that at least two distinct subpopulations of Leu 2+ cells are required for maximal suppression of an immune response, and that immunoregulatory circuits analogous to those described in mice exist in man. Future studies will be directed at determining whether selected defects in the suppressor-amplifier circuit occur in diseases characterized by disordered immunoregulation.