Abstract
ntroduction 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. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-γ -/- C57BL/6 mice, or anti-IFN-γ-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-γ-competent, IFN-γ -/-, or IFN-γR -/- CD8 + Tregs were used to evaluate the suppressive function of CD8 + ACAID Tregs in response to IFN-γ. IFN-γ -/- mice or mice treated with anti-IFN-γ antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-γ -/- ACAID CD8 + Tregs was restored through the administration of exogenous IFN-γ. This suppressive responsiveness toward IFN-γ was CD8 + Treg-intrinsic, as CD8 + Tregs from IFN-γR -/- mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-γ is not needed for the induction of CD8 + ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 475-483 |
| Number of pages | 9 |
| Journal | Journal of Leukocyte Biology |
| Volume | 91 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2012 |
Fingerprint
Keywords
- Anterior chamber
- Eye
- Immune privilege
- Interferon-gamma
- Local adoptive transfer
ASJC Scopus subject areas
- Cell Biology
- Immunology
Cite this
Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8 + T regulatory cells. / Paunicka, Kathryn; Chen, Peter W.; Niederkorn, Jerry Y.
In: Journal of Leukocyte Biology, Vol. 91, No. 3, 03.2012, p. 475-483.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8 + T regulatory cells
AU - Paunicka, Kathryn
AU - Chen, Peter W.
AU - Niederkorn, Jerry Y.
PY - 2012/3
Y1 - 2012/3
N2 - ntroduction 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. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-γ -/- C57BL/6 mice, or anti-IFN-γ-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-γ-competent, IFN-γ -/-, or IFN-γR -/- CD8 + Tregs were used to evaluate the suppressive function of CD8 + ACAID Tregs in response to IFN-γ. IFN-γ -/- mice or mice treated with anti-IFN-γ antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-γ -/- ACAID CD8 + Tregs was restored through the administration of exogenous IFN-γ. This suppressive responsiveness toward IFN-γ was CD8 + Treg-intrinsic, as CD8 + Tregs from IFN-γR -/- mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-γ is not needed for the induction of CD8 + ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.
AB - ntroduction 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. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-γ -/- C57BL/6 mice, or anti-IFN-γ-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-γ-competent, IFN-γ -/-, or IFN-γR -/- CD8 + Tregs were used to evaluate the suppressive function of CD8 + ACAID Tregs in response to IFN-γ. IFN-γ -/- mice or mice treated with anti-IFN-γ antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-γ -/- ACAID CD8 + Tregs was restored through the administration of exogenous IFN-γ. This suppressive responsiveness toward IFN-γ was CD8 + Treg-intrinsic, as CD8 + Tregs from IFN-γR -/- mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-γ is not needed for the induction of CD8 + ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.
KW - Anterior chamber
KW - Eye
KW - Immune privilege
KW - Interferon-gamma
KW - Local adoptive transfer
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U2 - 10.1189/jlb.0311173
DO - 10.1189/jlb.0311173
M3 - Article
VL - 91
SP - 475
EP - 483
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -