translation agency

Cutting edge: blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells.
Newell KA; He G; Guo Z; Kim O; Szot GL; Rulifson I; Zhou P; Hart J;
November 30, 1999
J Immunol. 1999 Sep 1;163(5):2358-62. Unique Identifier : AIDSLINE

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-gamma and TNF-alpha 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.

JOURNAL ARTICLE Animal Antigens, CD28/*IMMUNOLOGY Antigens, CD4/GENETICS Antigens, CD8/GENETICS Antigens, CD80/*IMMUNOLOGY Antigens, Differentiation/ADMINISTRATION & DOSAGE Cytokines/BIOSYNTHESIS CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Graft Rejection/GENETICS/IMMUNOLOGY/*PREVENTION & CONTROL Immunosuppressive Agents/*ADMINISTRATION & DOSAGE Injections, Intraperitoneal Intestine, Small/*TRANSPLANTATION *Lymphocyte Transformation/GENETICS/IMMUNOLOGY Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Th1 Cells/METABOLISM Th2 Cells/METABOLISM