Regulation of the cytotoxic T lymphocyte response against Qa-1 alloantigens

Spleen cells from B6.T1a^a (Qa-1^a) mice primed against C57BL/6 (Qa-1^b) splenocytes in vivo generate Qa-1-specific CTL when rechallenged with Qa-1^b Ag in vitro. The addition of unirradiated Qa-1^b splenocytes to these cultures inhibits the generation of Qa-1-specific CTL. By using highly purified cell populations, we demonstrate that the only cell population in resting spleen capable of causing this inhibition is NK1.1⁺. Although resting CD8 cells lack inhibitory activity, purified CD8 cells precultured with Con A and IL-2 inhibit anti-Qa-1 CTL. This inhibition is specific for the Qa-1^b Ag expressed on the inhibitor cells, is not due to cold target competition, and is thus similar to that ascribed to veto cells. Although NK cells from resting spleen inhibit the generation of Qa-1-specific CTL, NK cells precultured in the presence of Con A and IL-2 show an approximate 30-fold increase in veto activity. Thus, NK cells represent the most likely cell population for down-regulating anti-self class I-reactive CTL.