The induction of alloreactive cytotoxic responses in vivo are inhibited by pretreatment with M is-disparate cells.

Alloreactive cytotoxic cells (CTL) are subject to regulation. These experiments were designed to study the in vivo down-regulation of CTL. Mice injected with allogeneic lymphoid cells (responders) develop CTL that are assayed in vitro by their ability to lyse 51Cr-labeled target cells of an appropriate H-2 haplotype. However, if CBA/J responder mice (H-2k, mls d) are pretreated with spleen cells from C3H/HeN mice, which are H-2 compatible (H-2k) but Mis- and minor antigen-disparate (mis c), there is virtually complete inhibition of the ability to develop CTL against A/J cells (H-2a, mls c) in vivo. In a similar manner, pretreatment of CBA/J responders with B10.BR (H-2k, mls b) cells resulted in the inhibition of the CTL response against B10.A(4R) (H-2h4, mls b). The state of CTL responsiveness appears to be H-2 restricted and requires that the allogeneic cells used for immunization share minor histocompatibility antigens with the strain of mouse selected for pretreatment.