Mutual recognition of parental and F1 lymphocytes. II. Analysis of graft-vs-host-induced suppressor cell activity for T cell-mediated lympholysis to trinitrophenyl self and alloantigens.

Abstract

Spleen cells from (C57BL/10 x B10.A)F1 mice that had been injected 2 wk earlier with C57BL/10 (B10) or B10.A parental spleen cells were mixed with spleen cells from untreated F1 mice. The cell mixture was sensitized in vitro to trinitrophenyl-modified syngeneic cells (TNP-self) or alloantigens for a cell-mediated lympholysis (CML) response, and assayed for effector cell activity 5 days later. Cells from B10.A- but not B10-injected F1 spleens suppressed the CML of normal F1 spleens cells. In contrast, strong suppressive activity was obtained from irradiated B10-injected F1 mice. Thus, F1 mice were selectively resistant to GVH-associated immunosuppression induced by B10, but not by B10.A, parental spleen cells, and this F1 resistance mechanism appeared to be radiosensitive. The suppressive activity of spleen cells from irradiated, parental-injected F1 mice could be at least partially accounted for by cytotoxic activity of parental cells directed against alloantigens expressed by the F1. However, suppressor activity in intact parental-injected F1 mice appeared to be due to parental-induced F1 suppressor cells. The results are discussed with respect to: a) the use of this system as a possible model for investigating the selective resistance of F1 mice to parental T cell-induced GVH reactions, and b) the implications involved in the mutual recognition between F1 and parental lymphocytes, which may be relevant for immune surveillance against self-reactive T cell clones.