THE ROLE OF ENDOGENOUS GLUCOCORTICOIDS ON HOST T CELL POPULATIONS IN THE PERIPHERAL LYMPHOID ORGANS OF MICE WITH GRAFT-VERSUS-HOST DISEASE1
- 1 January 1996
- journal article
- Published by Wolters Kluwer Health in Transplantation
- Vol. 61 (1), 76-83
- https://doi.org/10.1097/00007890-199601150-00016
Abstract
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.Keywords
This publication has 27 references indexed in Scilit:
- Tissue-specific expression of heat shock proteins 70 and 90: potential implication for differential sensitivity of tissues to glucocorticoidsMolecular and Cellular Endocrinology, 1993
- Regulation of Glucocorticoid Receptor Function through Assembly of a Receptor‐Heat Shock Protein ComplexaAnnals of the New York Academy of Sciences, 1993
- Lymphokine synthesis in vivo in an acute murine graft-versus-host reaction: mRNA and protein measurements in vivo and in vitro reveal marked differences between actual and potential lymphokine production levelsInternational Immunology, 1993
- Peripheral clonal deletion of superantigen‐reactive T cells is enhanced by cortisoneEuropean Journal of Immunology, 1993
- Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn)Cell, 1991
- T cell antigen receptor activation pathways: The tyrosine kinase connectionCell, 1991
- Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunityCell, 1990
- The Vβ-specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal miceCell, 1989
- THE GRAFT-VERSUS-HOST REACTION AND IMMUNE FUNCTIONTransplantation, 1984
- Mutual recognition of parental and F1 lymphocytes. Selective abrogation of cytotoxic potential of F1 lymphocytes by parental lymphocytes.The Journal of Experimental Medicine, 1980