INTERMEDIATE TCR CELLS CAN INDUCE GRAFT-VERSUS-HOST-DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Mice fall victim to GVHD when subjected to immunosuppressive treatment and injected with allogeneic bone marrow cells. A major population of cells associated with GVHD is known to be T cells. However, whether s uch T cells are of thymic or extrathymic origin is obscure. We applied two immunosuppressive conditions, 9 and 6.5 Gy irradiation, to C3H/He mice (H-2(k)). Bone marrow cells for injection were obtained from C57 BL/6 (B6) mice (H-2(b)). The 9-Gy mice were reconstituted by lymphocyt es of donor origin and showed GVHD, whereas 6.5-Gy mice were reconstit ution by lymphocytes of recipient origin and showed mild GVHD The live r was the organ where the reconstitution of lymphocytes occurred effic iently, and a major lymphocyte subset was intermediate tint) CD3 cells (i.e., CD3(int) cells) in both mice. CD3(int) cells had the propertie s of extrathymic T cells, showing the phenotype of NK1.1(+)CD3(int) us ing invariant V alpha 14 chain. In 6.5-Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient origin. The sorted CD3(in t) cells from the Liver of 9-Gy mice evoked similar GVHD when transfer ed into 6.5-Gy irradiated C3H/He mice, These results suggest that CD3( int) cells of extrathymic origin are a major population for the induct ion of GVHD under immunosuppressive conditions. (C) 1998 Academic Pres s.