title: Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys.
abstract: Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Pavel
authors.initials: P
authors.lastname: Bostik
authors.forename: Shari N
authors.initials: SN
authors.lastname: Gordon
authors.forename: Lara
authors.initials: L
authors.lastname: Pereira
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Engram
authors.forename: Ann
authors.initials: A
authors.lastname: Mayne
authors.forename: Richard M
authors.initials: RM
authors.lastname: Dunham
authors.forename: Benton
authors.initials: B
authors.lastname: Lawson
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ratcliffe
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.forename: James
authors.initials: J
authors.lastname: Else
authors.forename: Keith
authors.initials: K
authors.lastname: Reimann
authors.forename: Silvija I
authors.initials: SI
authors.lastname: Staprans
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D049109:Cell Proliferation; D016665:Cercocebus atys / Q000097:blood* / Q000378:metabolism; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008954:Models, Biological; D009092:Mucous Membrane / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D019562:Viral Load; D014766:Viremia / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D011948:Receptors, Antigen, T-Cell