The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens

Daniel R. Saban, Janet Cornelius, Sharmila Masli, Johannes Schwartzkopff, Maire Doyle, Sunil K. Chauhan, Ammon B. Peck, Maria B. Grant

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2435-2442
Number of pages8
JournalMolecular vision
Volume14
StatePublished - Dec 19 2008
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology

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    Saban, D. R., Cornelius, J., Masli, S., Schwartzkopff, J., Doyle, M., Chauhan, S. K., Peck, A. B., & Grant, M. B. (2008). The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. Molecular vision, 14, 2435-2442.