title: Following EAU recovery there is an associated MC5r-dependent APC induction of regulatory immunity in the spleen.
abstract: OBJECTIVE
  IRBPp-specific regulatory immunity is found in the spleens of mice recovered from experimental autoimmune uveoretinitis (EAU). Induction of this regulatory immunity is dependent on the expression of the melanocortin 5 receptor (MC5r). Therefore, the authors investigated whether dependence on the expression of MC5r was with the T cells or with the APCs mediating protective regulatory immunity in the EAU-recovered mouse spleen.
  
  
  METHODS
  Wild-type and MC5r-/- mice were immunized to induce EAU. The IRBPp-stimulated T-cell response in spleens of wild-type and MC5r-/- mice were compared for surface markers and cytokine production. Spleen APC were isolated and used to stimulate cytokine production and regulatory activity in IRBP-specific T cells from wild-type or MC5r-/- mice assayed in culture by ELISA, by flow cytometry, and in vivo by adoptive transfer into EAU mice.
  
  
  RESULTS
  IRBPp-specific CD25+CD4+ T cells from spleens of EAU-recovered wild-type mice express a Treg cell phenotype of FoxP3 and TGF-β compared with the effector T-cell phenotype of IFN-γ and IL-17 production in EAU-recovered MC5r-/- mice. APCs from the spleens of wild-type mice recovering from EAU promoted regulatory T-cell activation in IRBP-specific effector T cells from the spleens of EAU-recovering MC5r-/- mice. Spleen APCs from EAU-recovering wild-type, but not MC5r-/-, mice induced TGF-β expression by primed IRBP-specific effector T cells.
  
  
  CONCLUSIONS
  Dependence on MC5r expression is with an APC that promotes or selectively activates IRBP-specific FoxP3+ TGF-β+ CD25+CD4+ Treg cells in the spleens of EAU-recovered mice.
authors: Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Darren J
authors: DJ
authors: Lee
authors: Andrew W
authors: AW
authors: Taylor
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D044101:Receptors, Melanocortin / Q000235:genetics* / Q000276:immunology*; D012173:Retinitis / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D044101:Receptors, Melanocortin; D012177:Retinol-Binding Proteins; D016212:Transforming Growth Factor beta; D000099214:Retinol-Binding Proteins, Interstitial; C498833:Foxp3 protein, mouse; C086971:melanocortin 5 receptor