THE ROLE OF ENDOGENOUS GLUCOCORTICOIDS ON HOST T-CELL POPULATIONS IN THE PERIPHERAL LYMPHOID ORGANS OF MICE WITH GRAFT-VERSUS-HOST DISEASE

Previously, we demonstrated that immature CD4(+)8(+) and mature CD4(+) thymocyte populations were selectively eliminated during murine graft -versus-host disease (GVHD) as a consequence of elevated levels of end ogenous glucocorticoids. In this report, we investigated whether the m arked reduction of GD4(+)8(+) and CD4(+) thymocyte populations would a ffect host CD4(+) and CD8(+) T cell populations in the spleens and lym ph nodes (LN) of mice undergoing GVHD. GVHD was induced in (C57BL/6xA) F1 (E6AF1) mice by injecting A strain parental lymphoid cells. Using a n antibody against H2K(b) antigens, labeled host B6AF1 cells were dist inguished from unlabeled donor A cells. Our results demonstrated a mar ked deficiency of host CD4(+) and CD8(+) T cells in the spleens and LN of GVHD mice on day 21 after GVHD induction. The severe reduction of host T cell populations in the peripheral lymphoid organs did not appe ar to result from the elimination of CD4(+)8(+) and CD4(+) thymocyte p opulations. However, adrenalectomy before GVHD induction reversed the severe loss of both host CD4(+) and CD8(+) T cell populations in the L N of GVHD mice on day 21, whereas cortisone treatment of adrenalectomi zed (ADX) GVHD mice resulted in reduction of host LN CD4(+) and CD8(+) T cell populations similar to that observed in non ADX GVHD animals o n day 21. In addition, adrenalectomy markedly improved the proliferati ve response of LN T cells to mitogens when compared with immunosuppres sed T cells from the LN of non ADX GVHD mice. In contrast, adrenalecto my did not reverse splenic T cell immunosuppression and the marked red uction of splenic host T cell. populations during GVHD. These results suggest that high levels of endogenous glucocorticoids during GVHD pla y a central role in mediating severe deficiency of host T cell populat ions and inducing severe T cell immunosuppression in the LN, but not i n the spleen, of GVHD mice.