title: The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens.
abstract: OBJECTIVE
  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-2(b)) mice received an intracameral (IC) inoculation with BALB/c (H-2(d)) 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.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA. daniel.saban@schepens.harvard.edu
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
authors.forename: Janet
authors.initials: J
authors.lastname: Cornelius
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwartzkopff
authors.forename: Maire
authors.initials: M
authors.lastname: Doyle
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens