The Relationship of Cell Division to the Generation of Cytotoxic Activity in Mixed Lymphocyte Culture

There is good evidence that the proliferative response of lymphocytes in the presence of allogeneic cells ("mixed lymphocyte response") is a reflection of specific recognition of alloantigens in vitro (1, 2) although the magnitude of the response is clearly influenced by nonspecific serum factors and the presence of' non-lymphoid cells in the cultures (3). One consequence of in vitro exposure of lymphocytes to irradiated or mitomycin-treated allogeneic cells is the production of cytotoxic cells which are specific for the sensitizing alloantigens (4). However, the relationship between the proliferative response in mixed lymphocyte cultures (MLC) and the development of' cytotoxic activity is not fully understood. It is now evident, for example, that the production of' cytotoxic cells is not an invarible consequence of strong proliferative responses in allogeneic mixed culture (5). Moreover, although the proliferative response to alloantigens is virtually unimpaired after adsorption of lymphocytes on allogeneic monolayers before MLC stimulation, this procedure results in a specifc reduction in the generation of cytotoxic cells after the MLC (6). This latter observation is consistent with the hypothesis that cytotoxic precursors may be distinct from cells that account for the bulk of proliferative activity in MLC. This hypothesis receives some support from the finding that high levels of cytotoxic activity may develop in the absence of substantial proliferative responses across certain histocompatabili ty barriers (7).