Cellular requirements for the induction of cytotoxic T cells in vitro.

The stimulator and accessory cell requirements for the induction of cytotoxic T cell responses to alloantigens in vitro are reviewed. The ability of lymphocytes to stimulate was acquired early in development and was found to be a property of both Ig+ and Ig- cells. The presence of Fc receptors, complement receptors or Ia antigens on lymphocytes did not confer superior stimulator capacity. In contrast to lymphocytes mature macrophages were poor stimulators. When resting lymphocytes were used as a source of stimulator cells there was an additional requirement for an adherent accessory cell population for the induction of cytotoxic T cells. The accessory cell population functioned whether syngeneic or allogeneic with the responder and was required for the induction rather than the maintenance of the response. It was further characterized as an Ig+, theta, FcR+/-, CR +/-, Ia- cell which was not a mature macrophage. Accessory cells could be replaced to some extent by supernatants from spleen cell cultures. A model for T cell induction is proposed where only cells which produce unique inductive stimuli are able to function as stimulator cells. Stimulator cells are defined as those cells capable of stimulating cytotoxic T cell precursors directly and independently. Stimulator capacity is suggested to be a function of activated cells only, thus lymphocytes only stimulate following activation by accessory cells. Cells lacking innate stimulator capacity but exhibiting Ia antigens are suggested to stimulate via an alternative means.