The Requirement for Dna Synthesis

The terminal step in the differentiation of those T lymphocytes that are capable of becoming cytotoxic effector cells ordinarily occurs when the effector cell precursors encounter foreign cell antigens in vivo for which they are presumably already committed . The in vitro analog for this final step, the mixed leukocyte culture (MLC)' reaction, makes possible a detailed analysis of cellular and molecular events accompanying the generation of cytotoxic function in T cells . It has been clearly established that the generation of cytotoxic effector cells in vitro is accompanied by extensive proliferation in the reacting cell population . Prevention of or interference with proliferation has a profound suppressive effect on development of a full cytotoxic response in vitro, as does selective elimination ofdividing cells during sensitization (1-3) . On the other hand, it has been shown by a number of investigators that proliferation of cells in response to alloantigenic stimulation is not in itself sufficient to develop a cytotoxic response (4, 5) . These studies, however, leave unanswered very important and fundamental biological questions . Is one or more rounds of cell division absolutely required for the differentiation of a resting T cell to the cytotoxic effector cell state? Or, is it the case that proliferation triggered by contact with cell-bound alloantigen serves simply to amplify a specific, already differentiated (cytotoxic) cell type within the general cell population? A second, related question is whether expression of new genetic information is required for initial development of cytotoxic function, or whether the transition from resting T cell to cytotoxic effector cell is regulated at some other level, for example requiring only a rearrangement of membrane components .