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




 

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



 




Information in this article was accurate in November 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.