THE ROLE OF CD4-HYBRID HOST IN THE RESISTANCE TO LETHAL GRAFT-VERSUS-HOST DISEASE INDUCTION BY TRANSFER OF PARENT SPLEEN-CELLS( AND CD8+ CELLS IN NORMAL F1)

Transfer of a certain number of C57BL/6 (B6) spleen cells into (BALB/c xB6)F-1 (CB6F(1)) nu/nu mice, which are deficient in T cells, causes l ethal graft-versus-host disease (GVHD) in the recipients. However, whe n normal CB6F(1) mice are used as recipients, lethal GVHD does not occ ur. Using this lethal GVHD system, we investigated which roles CD4(+) and CD8(+) T cells play in the resistance to lethal GVHD induction by parent cell transfer in the normal F-1 hybrid host. Lethal GVHD induct ion by B6 spleen cells in CB6F(1) nu/nu mice was blocked by prior reco nstitution of the recipients with normal syngeneic spleen cells. In ad dition, all nu/nu mice reconstituted with syngeneic CD8(+) spleen cell s developed lethal GVHD, whereas none of the nu/nu mice reconstituted with CD4(+) cells did. Both spleen weight and number of spleen cells i n the former prominently decreased in contrast to the slight increase (peak at 15 weeks) seen in the latter after transfer of donor spleen c ells. H-2D(d-) Thy1.2(+) cells, which are considered to derive from do nor B6 T cells, existed in the spleen from the CD4(+) spleen cell-reco nstituted GVHD mice, peaking at 5 weeks then gradually decreasing afte r transfer of donor cells. However, they disappeared in the normal spl een cell-reconstituted GVHD mice 5 weeks later. These findings suggest that CD4(+) cells in the normal F-1 hybrid host play a critical role in the resistance to lethal GVHD induction by parent spleen cell trans fer, although CD8(+) cells are required for the prompt elimination of donor cells.