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Role of IFN-? in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells.

ABSTRACT: 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-? is needed for the suppressive function of CD8+ ACAID Tregs. This study tested the hypothesis that IFN-? 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-?(-/-) C57BL/6 mice, or anti-IFN-?-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-?-competent, IFN-?(-/-), or IFN-?R(-/-) CD8+ Tregs were used to evaluate the suppressive function of CD8+ ACAID Tregs in response to IFN-?. IFN-?(-/-) mice or mice treated with anti-IFN-? antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-?(-/-) ACAID CD8+ Tregs was restored through the administration of exogenous IFN-?. This suppressive responsiveness toward IFN-? was CD8+ Treg-intrinsic, as CD8+ Tregs from IFN-?R(-/-) mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-? is not needed for the induction of CD8+ ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.

SUBMITTER: Paunicka K

PROVIDER: S-EPMC3289396 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Publications

Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells.

Paunicka Kathryn K Chen Peter W PW Niederkorn Jerry Y JY

Journal of leukocyte biology 20111216 3

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-γ is needed for the suppressive function of CD8+ ACAID Tregs. This study tested the hypothesis that IFN-γ is needed for alloantigen-specific ACAID CD8+ Tregs to execute their suppressive function but is not required for the establishment of ACAID CD8+ Tregs. ...[more]

PMID: 22180630

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Project description:Evaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-? secreting cells. However, T-cells are capable of producing many more functions than just IFN-?, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-? secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-? producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-? functions. Similarly, the extent of missed virus-specific responses in IFN-? ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-? secreting CD4+ and CD8+ cells were low. Proportions of IFN-? negative CD4+ expressing IL-2, Perforin, or TNF-? to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-? positive CD4+ (0 of 7) T-cell phenotype, p?=?0.02; Fisher's Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-? negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-?, was significantly higher in IFN-? negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-? positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-? producing cells but also among those T-cells that do not express IFN-?.

Dataset Information

Role of IFN-? in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells.

Publications

Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells.

Similar Datasets

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