REGULATION OF ALLOANTIGEN-MEDIATED T-CELL PROLIFERATION BY ENDOGENOUS INTERFERON-γ: Implications for Long-Term Allograft Acceptance: 1

AT Hassan, Z Dai, BT Konieczny, GH Ring… - …, 1999 - journals.lww.com
AT Hassan, Z Dai, BT Konieczny, GH Ring, FK Baddoura, LH Abou-Dahab, AA El-Sayed…
Transplantation, 1999journals.lww.com
Background. Recent data suggest that interferon (IFN)-γ 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-γ 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-γ+/+) and IFN-γ gene-knockout (IFN …
Abstract
Background.
Recent data suggest that interferon (IFN)-γ 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-γ 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-γ+/+) and IFN-γ gene-knockout (IFN-γ−/−) 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-γ 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-γ−/− mice than in IFN-γ+/+ 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-γ. In contrast, alloantigen-induced T lymphocyte apoptosis in vivo did not differ between IFN-γ+/+ and IFN-γ−/− mice, and T-cell costimulation blockade enhanced alloantigen-induced T-cell apoptosis in both mouse strains.
Conclusions.
These data suggest that endogenous IFN-γ 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.
Lippincott Williams & Wilkins