IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells.
Murine models indicate that interleukin-10 (IL-10) can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T-cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is up-regulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (NK) cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and -uninfected individuals. These data indicate that multiple cell types contribute to IL-10-mediated immune suppression in the presence of uncontrolled HIV viremia.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Mark A
MA
Brockman
Douglas S
DS
Kwon
Daniel P
DP
Tighe
David F
DF
Pavlik
Pamela C
PC
Rosato
Jennifer
J
Sela
Filippos
F
Porichis
Sylvie
S
Le Gall
Michael T
MT
Waring
Kristin
K
Moss
Heiko
H
Jessen
Florencia
F
Pereyra
Daniel G
DG
Kavanagh
Bruce D
BD
Walker
Daniel E
DE
Kaufmann
D049109:Cell Proliferation; D002478:Cells, Cultured; D004194:Disease; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D053701:Receptors, Interleukin-10 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D014766:Viremia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D012333:RNA, Messenger; D053701:Receptors, Interleukin-10; D016753:Interleukin-10