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CUTTING EDGE |
,,§
*
Department of Surgery,
Committee on Immunology,
Department of Pathology, and
§
Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637
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-
and TNF-
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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