Activation of Listeria monocytogenes-induced prekiller T cells by interleukin-2.

Thymus-dependent lymphocytes, or T cells, of rats infected with Listeria monocytogenes acquire a potent cytolytic capability when the cells are restimulated in vitro by Listeria antigens. Activation of such Listeria monocytogenes-dependent cytotoxic T lymphocytes requires both antigen and histocompatible accessory cells, but only when the responder T cells have been specifically depleted of lymphocytes that are responsive to accessory cell alloantigens. When unselected T cells are used, significant activation occurs in specific-antigen-free cultures containing allogeneic accessory cells. This seeming paradox is explained by the fact that a lymphokine generated in mixed leukocyte cultures can promote the terminal differentiation of cytotoxic T lymphocytes precursors. This lymphokine has tentatively been identified as interleukin-2. The results suggest that a three stage process is involved in the activation of Listeria monocytogenes-dependent cytotoxic T lymphocytes. The first stage occurs in response to an immunizing Listeria monocytogenes infection and itself involves two significant events, the polyclonal priming of prekiller cells and the generation of Listeria antigens-specific helper T cells. During the second stage, helper T cells are stimulated by Listeria antigens to release interleukin-2. This process is efficiently executed only in the presence of histocompatible accessory cells. The third stage in the activation process requires neither accessory cells nor antigen and involves the interleukin-2-driven differentiation of prekiller cells.