title: Central memory CD4 T cells are the predominant cell subset resistant to anergy in SIV disease resistant sooty mangabeys.
abstract: OBJECTIVE
  HIV infection in humans and experimental SIV infection in rhesus macaques leads to the loss of recall antigen responses, immunological anergy in CD4 T cells and AIDS. In contrast, natural infection in sooty mangabeys with SIV does not lead to disease despite high viral loads accompanied by resistance of their CD4 T cells to undergo immunological anergy. The objective of the study was to further elucidate the mechanisms that contribute to anergy resistance in CD4 T cells from sooty mangabeys and identify whether the anergy resistance is a function of a specific subset or the entire cell population.
  
  
  METHODS
  Susceptibility or resistance to anergy was analyzed in antigen specific and defined CD4 T cell subsets from peripheral blood of sooty mangabeys and rhesus macaques by using an in vitro anergy inducing protocol; expression of the anergy associated gene GRAIL was measured.
  
  
  RESULTS
  Antigen specific CD4 T cells from SIV disease resistant sooty mangabey are relatively resistant to the development of anergy. This resistance is associated with a lack of an upregulation of GRAIL. Conversely, rhesus macaque CD4 T cells are sensitive to anergy induction associated with upregulation of GRAIL. Furthermore the anergy resistant phenotype of sooty mangabey CD4 T cells predominantly resides in central memory cells defined either as CD4+CD45RA-CD62L+ or CD4+CD28+CD95+CCR7+.
  
  
  CONCLUSIONS
  The maintenance of recall responses in sooty mangabeys is associated with the resistance of central memory CD4 T cells to the induction of anergy which may represent an important mechanism underlying SIV disease resistance in this species.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. Pavel.Bostik@emory.edu
authors.forename: Pavel
authors.initials: P
authors.lastname: Bostik
authors.forename: Erika S
authors.initials: ES
authors.lastname: Noble
authors.forename: Ann E
authors.initials: AE
authors.lastname: Mayne
authors.forename: Lisa
authors.initials: L
authors.lastname: Gargano
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016665:Cercocebus atys / Q000276:immunology* / Q000821:virology; D017635:Clonal Anergy / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D008992:Monkey Diseases / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D006433:Hemocyanins; D044767:Ubiquitin-Protein Ligases; C032808:keyhole-limpet hemocyanin