Distinct alloantigens trigger proliferative or nonproliferative T lymphocyte activation in CBA/N, CBA/J, and C3H mice.

Lymphokine release and proliferation take place during one-way murine mixed leukocyte cultures (MLCs) when responder and stimulator cells differ in H-2 alloantigens, whereas a dissociation of these two functions can be observed where there are incompatibilities in non H-2 alloantigens, It is possible that this dissociation depends on different thresholds of activation of the two responses, or that some non H-2 alloantigens selectively activate lymphokine release or proliferation. To investigate this question we used H-2-matched CBA/N, CBA/J. C3H/HN, (CBA/N x CBA/J)F1, and (CBA/N x C3H/HN)F1 leukocytes, both as responder and stimulator cells. CBA/N mice and the male F1 hybrids obtained from CBA/N mothers carry an X-linked immune defect that results in an arrest of B lymphocyte maturation. In the majority of MLC combinations tested, migration inhibition factor (MIF) release and proliferation took place in parallel. However, CBA/N, but not F1 leukocytes, stimulated MIF release and not proliferation by CBA/J responders, whereas C3H/HN leukocytes stimulated proliferative responses but not MIF release by CBA/J responders. Since proliferation and MIF release have a similar threshold of activation, their dissociation indicates that different non-H-2 alloantigens can specifically activate distinct T cell functions. Moreover, previously unsuspected alloantigen differences between CBA/N and CBA/J are revealed by MIF release.