title: Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells.
abstract: SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4(+) T cells to SIV-negative animals resulted in rapid loss of CD4(+) T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Milush
authors.forename: Kiran D
authors.initials: KD
authors.lastname: Mir
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sundaravaradan
authors.forename: Shari N
authors.initials: SN
authors.lastname: Gordon
authors.forename: Jessica
authors.initials: J
authors.lastname: Engram
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Cano
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Reeves
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Anton
authors.forename: Eduardo
authors.initials: E
authors.lastname: O'Neill
authors.forename: Eboneé
authors.initials: E
authors.lastname: Butler
authors.forename: Kathy
authors.initials: K
authors.lastname: Hancock
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Cole
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: James G
authors.initials: JG
authors.lastname: Else
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016665:Cercocebus atys; D007252:Influenza Vaccines; D008070:Lipopolysaccharides / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018417:Th1 Cells / Q000821:virology; D058504:Th17 Cells / Q000821:virology; D018418:Th2 Cells / Q000821:virology; D019562:Viral Load
chemical_list: D007252:Influenza Vaccines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D062793:Occludin