| First Author | Konieczny BT | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 5 | Pages | 2059-64 |
| PubMed ID | 9498741 | Mgi Jnum | J:123738 |
| Mgi Id | MGI:3719346 | Doi | 10.4049/jimmunol.160.5.2059 |
| Citation | Konieczny BT, et al. (1998) IFN-gamma is critical for long-term allograft survival induced by blocking the CD28 and CD40 ligand T cell costimulation pathways. J Immunol 160(5):2059-64 |
| abstractText | It is postulated that IFN-gamma production hinders long-term acceptance of transplanted organs. To test this hypothesis, we compared survival of skin and heart allografts in wild-type (IFN-gamma+/+) mice to that in IFN-gamma gene knockout (IFN-gamma-/-) mice. We found that perioperative blockade of the CD28 and/or CD40 ligand T cell costimulation pathways induces long-term skin and heart allograft survival in IFN-gamma+/+ recipients but fails to do so in IFN-gamma-/- mice or in wild-type mice treated with IFN-gamma-neutralizing Ab at the time of transplantation. In vitro studies showed that endogenously produced IFN-gamma down-regulates T cell proliferation and CTL generation in MLCs. These actions of IFN-gamma were not mediated by TNF-alpha production or Fas-Fas ligand interactions. In vivo studies revealed exaggerated expansion and, subsequently, impaired deletion of superantigen-reactive T lymphocytes in IFN-gamma-/- mice injected with staphylococcal enterotoxin B. Taken together, our findings indicate that IFN-gamma does not hinder but instead facilitates induction of long-term allograft survival possibly by limiting expansion of activated T cells. |
