T cells and macrophages involved in the autologous mixed lymphocyte reaction are required for the response to conventional antigen

Several groups have demonstrated that human T cells can proliferate in response to autologous non-T cells in an autologous mixed lymphocyte reaction (AMLR). However, the relevance of this interaction to those occurring between T and non-T cells required for reactivity to conventional antigen is unclear. To examine this relationship, we have developed monoclonal antibodies directed against responder and stimulator cells participating in the AMLR. The results of our studies indicate that the AMLR is heterogeneous and reflects the proliferation of two distinct T cell populations in response to distinct stimulator cells. One population of autologous reactive T cells is activated by signals from cells contained in macrophage-depleted, B-enriched populations. Another population of T cells (9.8 ± 2.1% of normal peripheral blood T cells) bears a determinant depicted by the monoclonal antibody T-29. These T cells proliferate in response to signals from a subpopulation (37 ± 2.8% of peripheral blood macrophages) of HLA-DRw-bearing macrophages, which also display a 120,000-dalton determinant depicted by the macrophage-specific monoclonal antibody Mac-120. Removal of the macrophage-responsive T-29 ⁺ portion of autologous reactive T cells (BrdUrd + light, cytolysis with T-29) abrogates T-dependent reactivity to conventional antigens (Candida albicans, PPD, collagen) as measured by proliferation and lymphokine release. Removal of the Mac-120 ⁺ Mφ, which stimulate the T-29 ⁺ cells, also substantially reduced T-dependent reactivity to antigens. Thus, at least a portion of the self reactivity reflected by the AMLR appears to represent interactions occurring among cells and macrophages required for reactivity to conventional antigen.