Regulation of the human allogeneic proliferative response in vitro

Abstract

It has previously been shown that presensitized cells in culture medium release suppressor factors (SF) which can inhibit a primary mixed leukocyte reaction (MLA I). This occurs when the presensitized cells are resensitized with an HLA-DR-specific cell, which can be either the primary stimulator or any other DR-identical allogeneic cell. The autologous responders (SF producer cells) and certain allogeneic cells are suppressed, which suggests that restriction takes place. In this paper the effect of preincubation of responder or stimulator cells in SF has been studied: (1) When unprimed responders are preincubated with the suppressor supernates (SF) and tested in MLR I against several stimulators, the cells of the autologous SF producer and certain other allogeneic cells are always inhibited as already observed when SF was added directly to a mixed lymphocyte culture. (2) When the same stimulators are preincubated with the same SF and used as stimulators with the same responders (not preincubated) then inhibition is observed without restriction. This difference in behavior suggests the existence of at least two factors, one acting directly but only on some responders (restricted factor) and the other acting through stimulators on all responders. (3) Filtration of unprimed responders through glass wool (before SF preincubation and coculture with stimulators in MLR I) produces nonadherent T cells which are suppressed more after preincubation with SF than the same cells unfiltrated. This could be due to the existence of a subset of “acceptor” cells. (4) None of these factors has immunoglobulin characteristics. Their molecular weights are between 40 000 and 70 000 daltons.