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 endogenous glucocorticoids. In this report, we investigated whether the marked reduction of CD4+8+ and CD4+ thymocyte populations would affect host CD4+ and CD8+ T cell populations in the spleens and lymph nodes (LN) of mice undergoing GVHD. GVHD was induced in (C57BL/6 x A)F1 (B6AF1) mice by injecting A strain parental lymphoid cells. Using an antibody against H2Kb antigens, labeled host B6AF1 cells were distinguished from unlabeled donor A cells. Our results demonstrated a marked 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 appear to result from the elimination of CD4+8+ and CD4+ thymocyte populations. However, adrenalectomy before GVHD induction reversed the severe loss of both host CD4+ and CD8+ T cell populations in the LN of GVHD mice on day 21, whereas cortisone treatment of adrenalectomized (ADX) GVHD mice resulted in reduction of host LN CD4+ and CD8+ T cell populations similar to that observed in non-ADX GVHD animals on day 21. In addition, adrenalectomy markedly improved the proliferative response of LN T cells to mitogens when compared with immunosuppressed T cells from the LN of non-ADX GVHD mice. In contrast, adrenalectomy did not reverse splenic T cell immunosuppression and the marked reduction of splenic host T cell populations during GVHD. These results suggest that high levels of endogenous glucocorticoids during GVHD play a central role in mediating severe deficiency of host T cell populations and inducing severe T cell immunosuppression in the LN, but not in the spleen, of GVHD mice.
You-Ten
K E
KE
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Lapp
W S
WS
D000315:Adrenalectomy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005938:Glucocorticoids / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D005938:Glucocorticoids