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Kenneth A Newell, Gang He, Zhong Guo, Oliver Kim, Gregory L Szot, Ingrid Rulifson, Ping Zhou, John Hart, J Richard Thistlethwaite, Jeffrey A Bluestone, Cutting Edge: Blockade of the CD28/B7 Costimulatory Pathway Inhibits Intestinal Allograft Rejection Mediated by CD4+ But Not CD8+ T Cells, The Journal of Immunology, Volume 163, Issue 5, September 1999, Pages 2358–2362, https://doi.org/10.4049/jimmunol.163.5.2358
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Abstract
The 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.