The human autologous mixed lymphocyte reaction. I. Suppression by macrophages and T cells

The autologous mixed lymphocyte reaction (AMLR) is a proliferative response of T cells to signals from autologous non-T cells. The AMLR has been an enigma to immunologists because spontaneous proliferation of cells removed from the body is usually substantially less than that observed with a strong AMLR. However, the AMLR is thought to represent an important in vitro function, since it has the attributes of other immune responses, and it is abnormal in a variety of disease states thought to have an immune basis. We reasoned that if the AMLR represented a fundamental immune phenomenon, it should be subject to regulation. In the present study, we present evidence for suppression of the AMLR by macrophages and by T cells. Macrophages inhibited the T cell proliferation to (B + null) cells in a dose-dependent fashion and throughout the time course of the AMLR. Elimination of suppressor T cells by a specific antiserum led to an increase in the AMLR, which was again suppressed in a dose-dependent way by addition of the suppressive T cells. It may be concluded that the AMLR itself is subject to immune regulation and that the suppressive influences observed probably strongly inhibit the AMLR in vivo. Removal of the suppressive principles allows the maximal expression of the AMLR in vitro. We believe that our demonstration of regulation of the AMLR should remove the enigma associated with it and lead to a better understanding of normal cell-cell interactions as well as the basis for abnormalities in a variety of immune-mediated diseases.