The Role of ACAID and CD4+CD25+FOXP3+ Regulatory T Cells on CTL Function Against MHC Alloantigens

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The Role of ACAID and CD4+CD25+FOXP3+ Regulatory T Cells on CTL Function Against MHC Alloantigens

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Title: The Role of ACAID and CD4+CD25+FOXP3+ Regulatory T Cells on CTL Function Against MHC Alloantigens
Author: Cornelius, Janet; Schwartzkopff, Johannes; Doyle, Maire; Peck, Ammon B.; Saban, Daniel; Masli, Sharmila; Chauhan, Sunil Kumar; Grant, Maria B.

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Citation: Saban, Daniel R., Janet Cornelius, Sharmila Masli, Johannes Schwartzkopff, Maire Doyle, Sunil K. Chauhan, Ammon B. Peck, and Maria B. Grant. 2008. The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. Molecular Vision 14: 2435-2442.
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Abstract: Purpose: Anterior chamber associated immune deviation (ACAID) is an antigen-specific form of peripheral immune tolerance that is induced to exogenous antigens placed in the ocular anterior chamber, which leads to a suppression in delayed-type hypersensitivity (DTH). Considerable work has been done on ACAID induction to major histocompatibility (MHC) alloantigens. However, its role on cytotoxic T lymphocyte (CTL) activity is currently unknown. Methods: C57BL/6 (H-2b) mice received an intracameral (IC) inoculation with BALB/c (H-2d) splenocytes. Splenic CD4+ and CD8+ T cell populations were characterized by flow cytometry and proliferation assays during induction and expression phases of ACAID. Percentages of CD4+CD25+FoxP3+ T regulatory cells (Treg) were also followed. Lastly, CTL function was measured at various time points during ACAID expression, and Treg were added to identify potential alterations in CTL function. Results: CD4+ and CD8+ T cell percentages and proliferation increased in the spleen during ACAID induction but then sharply decreased in response to an allospecific immunization. Expression of ACAID also exhibited a significant drop in CTL function. However, while Treg expansion was observed, these cells did not directly mediate the CTL inhibition. Conclusions: ACAID mediates an inhibition of CTL function against MHC alloantigens. Furthermore, we found that ACAID induction leads to the expansion and proliferation of CD4+ and CD8+ T cells while ACAID expression is associated with a diminishment in T cell percentages due to proliferation impairment. Lastly, Treg also expand during ACAID induction. However, our data suggest that Treg do not directly inhibit CTL activity.
Published Version: http://www.molvis.org/molvis/
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605729/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879998

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