Central memory CD4 T cells are the predominant cell subset resistant to anergy in SIV disease resistant sooty mangabeys.
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.
Bostik
Pavel
P
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. Pavel.Bostik@emory.edu
Noble
Erika S
ES
Mayne
Ann E
AE
Gargano
Lisa
L
Villinger
Francois
F
Ansari
Aftab A
AA
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
D006433:Hemocyanins; D044767:Ubiquitin-Protein Ligases; C032808:keyhole-limpet hemocyanin