Autologous Mixed Lymphocyte Reaction in Man

Human peripheral T cells and T-cell Subpopulations defined with monoclonal antibodies of the OKT series were studied for the proliferative response on stimulation with autologous non-T cells or mitogen-activated T cells as stimulators in autologous mixed lymphocyte reaction (AMLR). T cells exhibited a vigorous proliferative response when stimulated with autologous non-T cells or activated T cells but not with unactivated T cells. The stimulatory capacity of non-T cells or activated T cells in AMLR was inhibited by prior treatment of stimulator cells with 7, 2 anti-human Ia framework-specific monoclonal antibody in the absence of complement. A BUdR and light technique was used to ablate proliferating T cells in response to either non-T cells or activated T cells in AMLR. The removal of T cells responding to autologous non-T cells left the responsiveness to autologous activated T cells relatively intact. Conversely, the removal of T cells responding to autologous activated T cells left the responsiveness 10 autologous non-T cells relatively intact. Thus T cells responding to autologous non-T cells appear to be distinct from those responding to autologous activated T cells in AMLR. Further analysis with OKT4 and OKT8 monoclonal antibodies showed that the major population responding to autologous non-T cells was contained in OKT4⁺ T cells and that responding to autologous activated-T cells was contained in OKT8⁺ T-cell subset. However, both OKT4⁺ and OKT8⁺ T-cell subsets responded by proliferation to non-T cells and activated T cells in allogeneic MLR. T cells selected after AMLR between T and non-T cells or T and activated T cells were treated with mitomycin and examined for their regulatory influence on the proliferative response of fresh autologous responder T cells. T cells selected from T and non-T AMLR augmented and those obtained from T and activated T AMLR suppressed the proliferative responses of fresh autologous T cells to phytohaemagglutinin and to autologous or allogeneic non-T cells in AMLR or allogeneic MLR. These findings indicate that in AMLR between T and non-T cells or T and activated T cells phenotypically distinct Subpopulations of T lymphocytes respond by proliferation and express distinct immunoregulatory functions.