Induction of nonspecific, proliferative dependent, suppressor T lymphocytes in human mixed lymphocyte cultures

Abstract

Previous studies in animals and man have supported the role of suppressor cells in the control of the humoral and cellular immune response to soluble antigens. In the present studies we characterized the induction of suppressor cells in human mixed lymphocyte culture (MLC) and the effect of these cells on proliferation in MLC. Purified (monocyte-free) responder (Ac) and mitomycin-treated allogeneic lymphocytes (Bx) were used to establish standard 6-day one-way MLC (AcBx). Cells were harvested from this MLC and were then tested for suppressor activity in a second MLC containing stimulator and responder lymphocytes (ABx) autologous to cells in the first MLC. Suppressor cells were generated in MLC (AcBx) which inhibited proliferation when added on Day 1 of the second MLC (ABx); 1.6 × 10 3 suppressor cells (AcBx) induced 50% suppression when cultured with 10 5 stimulator and 10 5 responder cells. Further studies demonstrated that (a) suppressor cells were T lymphocytes, (b) induction and manifestation of suppressor activity was dependent on proliferation, and (c) suppressor activity was not absolutely restricted by HLA-D compatibility of suppressor and responder cells nor by antigenic specificities. These data support the possibility that in man in the allogeneic immune response is controlled by the development of suppressor T cells. The nonspecific character of the suppressor cells generated in MLC suggest that the induction of suppressors in vivo by antigen(s) may under certain circumstances reduce generalized immune responsiveness.