Cutting Edge: Blockade of the CD28/B7 Costimulatory Pathway Inhibits Intestinal Allograft Rejection Mediated by CD4+ But Not CD8+ T Cells

Journal of Immunology - Tập 163 Số 5 - Trang 2358-2362 - 1999
Kenneth A. Newell1,2, Gang He1, Zhong Guo1, Oliver Kim3, Gregory L. Szot3, Ingrid C. Rulifson2, Ping Zhou1, John Hart3, J. Richard Thistlethwaite1,2, Jeffrey A. Bluestone4,2,3
1Department of Surgery
2§Committee on Immunology,
3Department of Pathology and
4§Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637

Tóm tắt

AbstractThe effect of blocking the CD28/B7 costimulatory pathway on intestinal allograft rejection was examined in mice. Murine CTLA4Ig failed to prevent the rejection of allografts transplanted into wild-type or CD4 knockout (KO) mice but did inhibit allograft rejection by CD8 KO recipients. This effect was associated with decreased intragraft mRNA for IFN-γ and TNF-α and increased mRNA for IL-4 and IL-5. This altered pattern of cytokine production was not observed in allografts from murine CTLA4Ig-treated CD4 KO mice. These data demonstrate that blockade of the CD28/B7 pathway has different effects on intestinal allograft rejection mediated by CD4+ and CD8+ T cells and suggest that these T cell subsets have different costimulatory requirements in vivo. The results also suggest that the inhibition of CD4+ T cell-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines.

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