title: Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals.
abstract: In HIV-1 infection elevated serum levels of interferon-α (IFN-α) and interleukin-10 (IL-10) are associated with immune hyperactivation and disease progression. Recently, coexpression of CD49b and LAG-3 was shown to identify Type 1 regulatory T (Tr1) cells, which secrete large amounts of the immunosuppressive cytokine IL-10. We analyzed the frequency of CD49b/LAG-3(+) Tr1 cells in the peripheral blood of HIV-infected individuals at different stages of the disease. We found increased levels of CD49b/LAG-3(+) Tr1 cells as well as IL-10 in HIV patients. With disease progression, Tr1 cells negatively correlate with frequency of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. However, elevated IL-10 levels could not be ascribed to the CD49b/LAG-3(+)Tr1 cell population. Moreover, we showed in vitro that IFN-α leads to an upregulation of IL-10 as well as CD49b/LAG-3(+) Tr1 cell counts in healthy controls, recapitulating effects observed in vivo during HIV infection. Our results suggest that overexpression of IFN-α during HIV infection drives the generation of CD49b/LAG-3(+) Tr1 cells and the immunosuppressive cytokine IL-10. Furthermore, it remains unclear whether elevated IL-10 levels are beneficial or detrimental in regard to disease progression.
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .
authors.forename: Kristina
authors.initials: K
authors.lastname: Koch
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .
authors.forename: Nora
authors.initials: N
authors.lastname: Koch
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .
authors.forename: Ute
authors.initials: U
authors.lastname: Sandaradura de Silva
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.affiliation: 2 University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze zur Wiesch
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .|3 German Center for Infection Research (DZIF) , Partner Site Bonn-Cologne, Cologne, Germany .
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .|3 German Center for Infection Research (DZIF) , Partner Site Bonn-Cologne, Cologne, Germany .
authors.forename: Pia
authors.initials: P
authors.lastname: Hartmann
authors.affiliation: 4 Institute of Human Virology, University of Maryland , Baltimore, Maryland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Romerio
authors.affiliation: 1 First Department of Internal Medicine, University of Cologne , Cologne, Germany .|3 German Center for Infection Research (DZIF) , Partner Site Bonn-Cologne, Cologne, Germany .
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D039421:Integrin alpha2 / Q000032:analysis*; D016898:Interferon-alpha / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C508609:IL10 protein, human; D039421:Integrin alpha2; D016898:Interferon-alpha; D016753:Interleukin-10; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human