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The Journal of Immunology, Vol 150, Issue 1 197-205, Copyright © 1993 by American Association of Immunologists
ARTICLES |
M Sykes, VS Abraham, MW Harty and DA Pearson
Transplantation Research Biology Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129.
We have recently demonstrated, in a fully MHC-mismatched murine bone marrow transplantation model, that administration of a short course of high dose IL-2 markedly diminishes graft-vs-host disease (GVHD) without compromising alloengraftment or the graft-vs-leukemia (GVL) effect of allogeneic T cells. We have now evaluated the mechanism of the dissociation of GVL and GVHD observed in this model. We demonstrate that CD4+ T cells were required to produce severe, acute GVHD in the fully MHC-mismatched plus minor histocompatibility Ag-mismatched A/J-- >B10 strain combination. The GVHD-producing activity of A/J CD4+ T cells administered without CD8+ T cells was inhibited by IL-2 treatment. In contrast, CD8+ T cells alone mediated the GVL effect observed in the EL4 leukemia/lymphoma model, and CD4+ cells did not contribute to this effect. This CD8-mediated GVL activity was not inhibited by IL-2 treatment. Because naive A/J CD8+ T cells administered without CD4+ T cells did not produce acute GVHD, we were unable to evaluate the effect of IL-2 in this model. However, when A/J donors were presensitized with B10 skin grafts, CD4-depleted A/J spleen cells were capable of causing acute GVHD in B10 recipients. This CD8- mediated GVHD was not inhibited by treatment with IL-2. However, IL-2 did partially inhibit the GVHD produced by nondepleted presensitized A/J spleen cells, probably due to selective inhibition of the function of presensitized A/J CD4+ T cells. The dissociation of GVHD and GVL against the EL4 leukemia/lymphoma in IL-2-treated mice can therefore be explained by selective inhibition by IL-2 of CD4 activity.
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F. Lan, D. Zeng, P. Huie, J. P. Higgins, and S. Strober Allogeneic bone marrow cells that facilitate complete chimerism and eliminate tumor cells express both CD8 and T-cell antigen receptor-{alpha}{beta} Blood, June 1, 2001; 97(11): 3458 - 3465. [Abstract] [Full Text] [PDF]
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H. Ohdan, K. G. Swenson, H. S. Kruger Gray, Y.-G. Yang, Y. Xu, A. D. Thall, and M. Sykes Mac-1-Negative B-1b Phenotype of Natural Antibody-Producing Cells, Including Those Responding to Gal{alpha}1,3Gal Epitopes in {alpha}1,3-Galactosyltransferase-Deficient Mice J. Immunol., November 15, 2000; 165(10): 5518 - 5529. [Abstract] [Full Text] [PDF]
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Y.-G. Yang, J. J. Sergio, D. A. Pearson, G. L. Szot, A. Shimizu, and M. Sykes Interleukin-12 Preserves the Graft-Versus-Leukemia Effect of Allogeneic CD8 T Cells While Inhibiting CD4-Dependent Graft-Versus-Host Disease in Mice Blood, December 1, 1997; 90(11): 4651 - 4660. [Abstract] [Full Text] [PDF]
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 J. Ferrara, K. Cooke, L Pan, and W Krenger The immunopathophysiology of acute graft-versus-host-disease Stem Cells, September 1, 1996; 14(5): 473 - 489. [Abstract]
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