Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys.
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.
Klatt
Nichole R
NR
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Villinger
Francois
F
Bostik
Pavel
P
Gordon
Shari N
SN
Pereira
Lara
L
Engram
Jessica C
JC
Mayne
Ann
A
Dunham
Richard M
RM
Lawson
Benton
B
Ratcliffe
Sarah J
SJ
Sodora
Donald L
DL
Else
James
J
Reimann
Keith
K
Staprans
Silvija I
SI
Haase
Ashley T
AT
Estes
Jacob D
JD
Silvestri
Guido
G
Ansari
Aftab A
AA
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*
D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D011948:Receptors, Antigen, T-Cell