AN ACQUIRED TYPE OF REFRACTORINESS TO GRAFT-VERSUS-HOST REACTION IN ADULT F1 HYBRID MICE

1. Adult (C57BL × CBA)F1 mice which had been injected 22-50 days previously with C57BL spleen cells did not develop graft-versus-host (GVH) reaction following a subsequent injection of either C57BL or CBA spleen cells, in experiments where GVH reaction was assessed by means of the carbon clearance test of RE function. A first injection of CBA cells did not impair the onset of GVH reaction following a second injection of CBA cells, but induced partial or total impairment of the effect of C57BL cells. 2. The refractory state induced in (C57BL × CBA)F1 mice by C57BL cells towards GVH reaction evoked by a second injection of C57BL spleen cells could not be transferred passively by serum or adoptively by spleen cells. 3. Evidence of persistent C57BL donor anti-host activity was obtained by discriminant spleen assays. Activity was not detectable in similar assays of CBA cells, although the persistence of GVH reaction was strongly suggested in many cases by splenomegaly and raised phagocytic index. 4. Cytological analysis shows that previous injection of C57BL or CBA/H-T6 spleen cells into (C57BL × CBA/H-T6)F1 mice can inhibit proliferation of a second injection of donor cells when these belong to the other parental genotype. 5. It is considered that C57BL spleen cells cannot provoke a detectable GVH reaction in (C57BL × CBA)F1 mice when the spleen and lymphoid tissue have been extensively repopulated by C57BL cells. The persistence of first donor-type cells which are still active against the host probably determines the observed inhibitory effect on the subsequently injected spleen cells of the other parental genotype.