title: CD4+CD25+ T regulatory cells from FIV+ cats induce a unique anergic profile in CD8+ lymphocyte targets.
abstract: BACKGROUND
  Using the FIV model, we reported previously that CD4+CD25+ T regulatory (Treg) cells from FIV+ cats are constitutively activated and suppress CD4+CD25- and CD8+ T cell immune responses. In an effort to further explore Treg-mediated suppression, we asked whether Treg cells induce anergy through the alteration of production of cyclins, cyclin-dependent kinases and their inhibitors.
  
  
  RESULTS
  Lymphocytes were obtained from control or FIV+ cats and sorted by FACS into CD4+CD25+ and CD8+ populations. Following co-culture with CD4+CD25+ cells, CD8+ targets were examined by Western blot for changes in cyclins D3, E and A, retinoblastoma (Rb) protein, as well as the cyclin dependent kinase inhibitor p21cip1. Following co-culture with CD4+CD25+cells, we observed up-regulation of p21cip1 and cyclin E, with down-regulation of cyclin D3, in CD8+ cells from FIV+ cats. As expected, CD8+ targets from control cats were quiescent with little up-regulation of p21cip1 and cyclin E. There was also a lack of Rb phosphorylation in CD8+ targets consistent with late G1 cell cycle arrest. Further, IL-2 mRNA was down regulated in CD8+ cells after co-culture with CD4+CD25+ Treg cells. Following CD4+CD25+ co-culture, CD8+ targets from FIV+ cats also had increased Foxp3 mRNA expression; however, these CD8+Foxp3+ cells did not exhibit suppressor function.
  
  
  CONCLUSIONS
  Collectively, these data suggest that CD4+CD25+ Treg cells from FIV+ cats induce CD8+ anergy by disruption of normal G1 to S cell cycle progression.
authors.affiliation: North Carolina State University, College of Veterinary Medicine, Immunology Program, Department of Population Health and Pathobiology, 4700 Hillsborough Street, Raleigh, NC 27606, USA. mary_tompkins@ncsu.edu
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Fogle
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Tompkins
authors.forename: Mary B
authors.initials: MB
authors.lastname: Tompkins
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002415:Cats; D002453:Cell Cycle / Q000276:immunology; D017635:Clonal Anergy; D018920:Coculture Techniques; D015536:Down-Regulation; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016089:Immunodeficiency Virus, Feline; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit