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Transplantation. 1999 Jul 15;68(1):124-9.

Regulation of alloantigen-mediated T-cell proliferation by endogenous interferon-gamma: implications for long-term allograft acceptance.

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  • 1The Carlos and Marguerite Mason Transplantation Research Center, Department of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA.

Abstract

BACKGROUND:

Recent data suggest that interferon (IFN)-gamma is not an essential mediator of acute rejection but, instead, is critical for the induction of long-term allograft acceptance. The in vivo mechanisms by which endogenous IFN-gamma regulates the alloimmune response and thus facilitates the induction of long-term allograft survival are not known.

METHODS:

We examined long-term cardiac and skin allograft survival, alloantigen-induced T-cell proliferation, and alloantigen-induced T-cell apoptosis in wild-type (IFN-gamma+/+) and IFN-gamma gene-knockout (IFN-gamma-/-) mice treated with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte transfusion.

RESULTS:

We found that IFN-gamma is essential for long-term allograft survival induced by treating mice with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte transfusion. Alloantigen-induced T-cell proliferation in vivo was significantly greater in IFN-gamma-/- mice than in IFN-gamma+/+ mice, and T-cell costimulation blockade abrogated alloantigen-induced T-cell proliferation in wild-type mice but failed to do so in mice that lack IFN-gamma. In contrast, alloantigen-induced T lymphocyte apoptosis in vivo did not differ between IFN-gamma+/+ and IFN-gamma-/- mice, and T-cell costimulation blockade enhanced alloantigen-induced T-cell apoptosis in both mouse strains.

CONCLUSIONS:

These data suggest that endogenous IFN-gamma facilitates the induction of long-term allograft survival by limiting the proliferation of alloactivated T lymphocytes. The data also suggest that B7-CD28 T-cell costimulation blockade exerts immunosuppressive actions by inhibiting the proliferation of activated T lymphocytes and by promoting their apoptosis.

PMID:
10428279
[PubMed - indexed for MEDLINE]
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