Regulation of the cytotoxic T cell response to minor histocompatibility antigens.

A system is described in which the regulation of the cytotoxic T cell response to minor histocompatibility antigens can be analyzed. Killer precursor cells are derived from spleen cells of mice previously primed in vivo with minor H antigens; at low cell numbers, the helper activity in primed spleen cell populations is diluted away leaving a population of killer precursor cells which is relatively deficient in helper activity. Addition to these cultures of irradiated helper cells which have been generated in vitro allows induction of a strong cytotoxic response to minor H antigens. This helper function is mediated by specifically induced radioresistant T lymphocytes; the helper cells may recognize Mls antigens. In the same system, culture of higher numbers of primed responder cells yields a cytotoxic response which can be inhibited by irradiated suppressor cells which have been generated in vitro. These suppressor cells are also specifically induced T lymphocytes capable of radioresistant function; they appear to be generated only from populations of primed spleen cells. The fact that in the above system both cytotoxic T cells and suppressor T cells are obtained only from primed cells, while helper cells may be generated from unprimed cells, suggests a difference between these cells in specificity, induction requirements, or both. The suppressor cells must be present within the first 24 to 48 hr of culture; after this point, the differentiating cytotoxic response becomes resistant to suppressive effects.