Cutting edge: Blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4(+) but not CD8(+) T cells

The effect of blocking the CD28/B7 costimulatory pathway on intestinal allo graft. rejection was examined in mice, Murine CTLA4Ig faded to prevent the rejection of allografts transplanted into wild-type or CD4 knockout (KO) mi ce hut did inhibit allograft rejection by CDS KO recipients. This effect: w as associated with decreased intragraft mRNA for IFN-gamma and TNF-cr and i ncreased mRNA for IL-4 and IL-5. This altered pattern of cytokine productio n was not observed in allografts from murine CTLA4Ig-treated CD4 KO mice. T hese data demonstrate that blockade of the CD28/B7 pathway has different ef fects on intestinal allograft rejection mediated by CD4(+) and CD8(+) T cel ls and suggest that these T cell subsets have different costimulatory requi rements in vivo, The results also suggest that the inhibition of CD4+ T cel l-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines.