The Journal of Immunology, Vol 154, Issue 8 3713-3725, Copyright © 1995 by American Association of Immunologists

ARTICLES

Characterization of the autoreactive T cell repertoire in cyclosporin- induced syngeneic graft-versus-host disease. A highly conserved repertoire mediates autoaggression

AC Fischer, PP Ruvolo, R Burt, LR Horwitz, EC Bright, JM Hess, WE Beschorner and AD Hess
Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.

Syngeneic graft-vs-host disease (SGVHD) is a MHC class II-restricted T cell-mediated autoimmune syndrome that occurs following syngeneic bone marrow transplantation and the administration of cyclosporin (CsA). The present studies evaluated the V beta repertoire of T lymphocytes that mediate SGVHD. To facilitate analysis, SGVHD effector cells were adoptively transferred into thymectomized syngeneic recipients reconstituted with T cell-depleted bone marrow to provide an environment that allows for the selective clonal expansion of autoreactive T cells. Analysis of target tissues and PBL by reverse transcriptase PCR using oligonucleotide V beta-specific primers revealed a predominance of V beta 8.5+ T cells and a minor population expressing V beta 10. The majority of infiltrating lymphocytes in target tissues was confirmed to be V beta 8.5+ by in situ hybridization and by immunoperoxidase staining. A small population of V beta 10+ cells could also be detected. Furthermore, SGVHD effector T splenocytes depleted of lymphocytes expressing either the TCR-alpha beta or the V beta 8.5 determinant could not adoptively transfer SGVHD. Depletion of T cells expressing the V beta 10 determinant delayed the onset of this autoaggression syndrome. Subset analysis of the autoreactive T cell compartment revealed that the V beta 8.5 determinant was expressed on both CD4+ and CD8+ lymphocytes whereas the V beta 10 determinant was principally expressed on a minor population of CD4+ autoreactive T cells. These data were confirmed by limiting dilution analysis. Additional studies examining the effect of CsA on thymic differentiation revealed that although V beta 8.5 is not normally clonally deleted, there was a pronounced shift in the expression of this determinant between CD4 and CD8 single positive thymocytes, suggesting that CsA may inhibit normal positive selection processes for MHC class I and class II reactive T cells.

This article has been cited by other articles:

				J. S. Bryson, L. Zhang, S. W. Goes, C. D. Jennings, B. E. Caywood, S. L. Carlson, and A. M. Kaplan CD4+ T Cells Mediate Murine Syngeneic Graft-versus-Host Disease-Associated Colitis J. Immunol., January 1, 2004; 172(1): 679 - 687. [Abstract] [Full Text] [PDF]

				Y. Miura, C. J. Thoburn, E. C. Bright, W. Chen, S. Nakao, and A. D. Hess Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon gamma may be critical mediators for the development of autologous GVHD Blood, September 18, 2002; 100(7): 2650 - 2658. [Abstract] [Full Text] [PDF]

				W. Chen, C. Thoburn, and A. D. Hess Characterization of the Pathogenic Autoreactive T Cells in Cyclosporine-Induced Syngeneic Graft-Versus-Host Disease J. Immunol., December 15, 1998; 161(12): 7040 - 7046. [Abstract] [Full Text] [PDF]

				A. D. Hess, E. C. Bright, C. Thoburn, G. B. Vogelsang, R. J. Jones, and M. J. Kennedy Specificity of Effector T Lymphocytes in Autologous Graft-Versus-Host Disease: Role of the Major Histocompatibility Complex Class II Invariant Chain Peptide Blood, March 15, 1997; 89(6): 2203 - 2209. [Abstract] [Full Text] [PDF]