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 E. 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

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Histocompatibility
Isoantigens
Anterior Chamber
Cytotoxic T-Lymphocytes
Regulatory T-Lymphocytes
T-Lymphocytes
Peripheral Tolerance
Antigens
Immune Tolerance
Delayed Hypersensitivity
Immunization
Flow Cytometry
Spleen
Cell Proliferation

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Saban, D. R., Cornelius, J., Masli, S., Schwartzkopff, J., Doyle, M. E., Chauhan, S. K., ... 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.

The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. / Saban, Daniel R.; Cornelius, Janet; Masli, Sharmila; Schwartzkopff, Johannes; Doyle, Maire E.; Chauhan, Sunil K.; Peck, Ammon B.; Grant, Maria B.

In: Molecular Vision, Vol. 14, 19.12.2008, p. 2435-2442.

Research output: Contribution to journalArticle

Saban, DR, Cornelius, J, Masli, S, Schwartzkopff, J, Doyle, ME, Chauhan, SK, Peck, AB & Grant, MB 2008, 'The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens', Molecular Vision, vol. 14, pp. 2435-2442.
Saban DR, Cornelius J, Masli S, Schwartzkopff J, Doyle ME, Chauhan SK et al. The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. Molecular Vision. 2008 Dec 19;14:2435-2442.
Saban, Daniel R. ; Cornelius, Janet ; Masli, Sharmila ; Schwartzkopff, Johannes ; Doyle, Maire E. ; Chauhan, Sunil K. ; Peck, Ammon B. ; Grant, Maria B. / The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. In: Molecular Vision. 2008 ; Vol. 14. pp. 2435-2442.
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AU - Schwartzkopff, Johannes

AU - Doyle, Maire E.

AU - Chauhan, Sunil K.

AU - Peck, Ammon B.

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