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 such 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-2k). Bone marrow cells for injection were obtained from C57BL/6 (B6) mice (H-2b). The 9-Gy mice were reconstituted by lymphocytes of donor origin and showed GVHD, whereas 6.5-Gy mice were reconstituted by lymphocytes of recipient origin and showed mild GVHD. The liver was the organ where the reconstitution of lymphocytes occurred efficiently, and a major lymphocyte subset was intermediate (int) CD3 cells (i.e., CD3intcells) in both mice. CD3intcells had the properties of extrathymic T cells, showing the phenotype of NK1.1+CD3intusing invariant Vα14 chain. In 6.5-Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient origin. The sorted CD3intcells from the liver of 9-Gy mice evoked similar GVHD when transferred into 6.5-Gy irradiated C3H/He mice. These results suggest that CD3intcells of extrathymic origin are a major population for the induction of GVHD under immunosuppressive conditions.