| First Author | Paunicka K | Year | 2012 |
| Journal | J Leukoc Biol | Volume | 91 |
| Issue | 3 | Pages | 475-83 |
| PubMed ID | 22180630 | Mgi Jnum | J:181507 |
| Mgi Id | MGI:5311531 | Doi | 10.1189/jlb.0311173 |
| Citation | Paunicka K, et al. (2012) Role of IFN-gamma in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells. J Leukoc Biol 91(3):475-83 |
| abstractText | Introduction of alloantigens into the AC induces a form of immune tolerance known as ACAID, which induces antigen-specific CD8(+) Tregs, contributing to ocular immune privilege by down-regulating immune responses. Recent evidence suggests IFN-gamma is needed for the suppressive function of CD8(+) ACAID Tregs. This study tested the hypothesis that IFN-gamma is needed for alloantigen-specific ACAID CD8(+) Tregs to execute their suppressive function but is not required for the establishment of ACAID CD8(+) Tregs. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-gamma(-/-) C57BL/6 mice, or anti-IFN-gamma-treated WT C57BL/6 mice. LAT assays using C57BL/6 APCs as stimulators, CD4(+) T cells from C57BL/6 mice previously immunized toward BALB/c alloantigens as effector cells, and IFN-gamma-competent, IFN-gamma(-/-), or IFN-gammaR(-/-) CD8(+) Tregs were used to evaluate the suppressive function of CD8(+) ACAID Tregs in response to IFN-gamma. IFN-gamma(-/-) mice or mice treated with anti-IFN-gamma antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-gamma(-/-) ACAID CD8(+) Tregs was restored through the administration of exogenous IFN-gamma. This suppressive responsiveness toward IFN-gamma was CD8(+) Treg-intrinsic, as CD8(+) Tregs from IFN-gammaR(-/-) mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-gamma is not needed for the induction of CD8(+) ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses. |
