Immunoglobulin secretion in the human autologous mixed leukocyte reaction. Definition of a suppressor-amplifier circuit using monoclonal antibodies.

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Abstract
Induction of Ig synthesis in the autologous MLR [mixed leukocyte reaction] has an absolute requirement for helper/inducer (Leu-3) T cells, whereas an excess of suppressor/cytotoxic (Leu-2) cells suppresses the response. An effort was made to assess the immunoregulatory potential of T cells activated in the autologous MLR. T cells were cultured with autologous non-T cells for 8-9 d [days], after which the activated T cells were fractionated into subsets with monoclonal antibodies to T cell markers and HLA-DR antigen. Each population was co-cultured in fresh autologous MLR, and on the 8th day of culture, Ig-secreting cells were measured in a reverse hemolytic plaque assay. Activated Leu-2, DR+T cells, but neither Leu-2,DR- nor Leu-3 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. In the absence of Leu-2 cells in the 2nd 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. At least 2 distinct subpopulations of Leu-2 cells are required for maximal suppression of an immune response, and immunoregulatory circuits analogous to those described in the mouse apparently exist in man.

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