T Cell Ontogeny: Acquisition of a Functional Program

Abstract

Three discrete stages of thymocyte activation and maturation have been defined in an in vitro thymocyte culture system. The major population of immature cortical thymocytes (T3LT4+ T8+ T6+), which were previously considered to be unresponsive dead end cells, could be fully activated through the T11 molecule provided accessory cells were present. These results suggest that the T3LT4+T8+T6+ cell is a viable intermediate in thymic maturation. Furthermore, the development of functionally competent subsets was also regulated by accessory cells and could be blocked by the presence of anti-class II antibodies. Ia+ adherent cells promoted the development of the T4+T8– inducer subset, whereas cytotoxic T8+T4– cells predominated in the absence of accessory cells. In addition to cytotoxic and inducer T cell subsets, T cell receptor complex (T3–Ti)-positive cells bearing the NKH1 antigen arose at a later time in thymocyte culture. These NKH1+ cells exhibited NK activity and their development could be suppressed by adherent cells. We believe that this thymocyte culture system has permitted the isolation and identification of some of the events involved in the acquisition of a mature T cell phenotype and functional program. The identification and isolation of thymic subsets and cell to cell interactions provide new insights into the role of the major histocompatibility complex and accessory cell function during thymic maturation.