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Abstract
Chemokines play a critical role in the acute transplant rejection. In order to provide
an overview of the chemokine expression during the course of acute allograft rejection,
the intragraft expression profile of 11 chemokines representative of all four chemokine
subfamilies was analyzed in a murine skin transplantation model of acute rejection.
It was found that RANTES/CCL5, TARC/CCL17 and FKN/CX(3)CL1 were expressed at equivalent
levels in iso- and allografts. However, the other eight chemokines expression was
up-regulated to some extent in allograft compared with that in isograft. The levels
of MIP-1alpha/CCL3, MIP-3alpha/CCL20 and CTACK/CCL27 were progressively increased
from early stage (day 3 post-transplantation) to late stage (day 11). Mig/CXCL9, IP-10/CXCL10,
I-TAC/CXCL11, CXCL16 and LTN/XCL1 expression was elevated at middle stage (day 7),
and peaked at late stage. Among the up-regulated chemokines, I-TAC was the most obviously
elevated chemokine. Therefore, the effect of I-TAC on the skin acute allograft rejection
was evaluated. Block of I-TAC by the intradermal injection of anti-I-TAC monoclonal
antibody (mAb) reduced the number of CXCR3(+) cells in skin allograft and significantly
prolonged the skin allograft survival. The mAb treatment did not influence the proliferation
of the intragraft infiltrating cells in response to the allogeneic antigens, but significantly
decreased the number of the infiltrating cells and consequently lowered the secretion
of IFN-gamma and TNF-alpha. These data indicate I-TAC might be a dominant chemokine
involved in the intradermal infiltration and I-TAC-targeted intervening strategies
would have potential application for the alleviation of acute transplant rejection.