INVOLVEMENT OF BOTH DONOR CYTOTOXIC T-LYMPHOCYTES AND HOST NK1.1(-CELLS IN THE THYMIC ATROPHY OF MICE SUFFERING FROM ACUTE GRAFT-VERSUS-HOST DISEASE() T)

It has been reported that a dramatic decrease in the number of thymocy tes (thymic atrophy) in mice suffering from acute graft-versus-host di sease (GVHD) is ascribed to glucocorticoids. In this study, we examine d the possibility that cellular immune responses may thus be involved in thymic atrophy. In contrast to chronic GVHD mice, acute GVHD (C57BL /6 x DBA/2) Fl (BDF1) hybrid mice, which were injected intravenously w ith both spleen and lymph node cells from C57BL/6 mice, showed a drama tic decrease in the number of CD4 CD8 double-positive thymocytes 2 or 3 weeks after the induction of GVHD. A flow cytometric analysis reveal ed the donor-derived T cells with either CD4 or CD8 molecules to infil trate the thymus of the mice undergoing acute GVHD for 10 days. In a c ytolytic assay, such thymus-containing cells exhibited a cytolytic act ivity specific to the host cells. In addition. anti-H-2(d) cytolytic T cells showed a high level of cytolytic activity against BDF1 (H-2(bxd )) thymocytes, whereas they also showed a low level of cytolytic activ ity against C57BL/6 (H-2(b)) thymocytes, thus suggesting that the thym us-infiltrating donor-derived T cells killed the host thymocytes throu gh both anti-H-2(d)-specific and non-specific mechanisms. Interestingl y, a flow cytometric analysis revealed both the percentage and the abs olute cell number of host-derived NK1.1(+) CD3(+) cells to increase in the thymus of mice suffering from acute GVHD for 10 days. In addition , they also showed the cytolytic activity against YAC-1 cells and the mRNA expression of interleukin-12 (IL-12) in the thymus to be also sig nificantly augmented on day 7 after the induction of acute GVHD. Colle ctively, our results indicate that the cellular immune responses such as donor cytotoxic T lymphocytes and host NK1.1(+) T cells are therefo re involved in the thymic atrophy of mice suffering from acute GVHD.