title: IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses.
abstract: A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs), suppresses adaptive immune responses and inflammation in mice. In this study, we examined the role of IL-10-producing B cells in HIV-1 infection. Compared to uninfected controls, IL-10-producing B cell frequencies were elevated in both blood and sigmoid colon during the early and chronic phase of untreated HIV-1 infection. Ex vivo IL-10-producing B cell frequency in early HIV-1 infection directly correlated with viral load. IL-10-producing B cells from HIV-1 infected individuals were enriched in CD19(+)TIM-1(+) B cells and were enriched for specificity to trimeric HIV-1 envelope protein. Anti-retroviral therapy was associated with reduced IL-10-producing B cell frequencies. Treatment of B cells from healthy donors with microbial metabolites and Toll-like receptor (TLR) agonists could induce an IL-10 producing phenotype, suggesting that the elevated bacterial translocation characteristic of HIV-1 infection may promote IL-10-producing B cell development. Similar to regulatory B cells found in mice, IL-10-producing B cells from HIV-1-infected individuals suppressed HIV-1-specific T cell responses in vitro, and this suppression is IL-10-dependent. Also, ex vivo IL-10-producing B cell frequency inversely correlated with contemporaneous ex vivo HIV-1-specific T cell responses. Our findings show that IL-10-producing B cells are induced early in HIV-1 infection, can be HIV-1 specific, and are able to inhibit effective anti-HIV-1 T cell responses. HIV-1 may dysregulate B cells toward Bregs as an immune evasion strategy.
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhan
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kiera
authors.initials: K
authors.lastname: Clayton
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hanqi
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Erika
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jin Chao
authors.initials: JC
authors.lastname: Cao
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Blake
authors.initials: B
authors.lastname: Ziegler
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gregor
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Feng Yun
authors.initials: FY
authors.lastname: Yue
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sonya
authors.initials: S
authors.lastname: MacParland
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hai Han
authors.initials: HH
authors.lastname: Song
authors.affiliation: Maple Leaf Clinic, Toronto, Ontario, Canada.
authors.forename: Erika
authors.initials: E
authors.lastname: Benko
authors.affiliation: Maple Leaf Clinic, Toronto, Ontario, Canada.
authors.forename: Gabor
authors.initials: G
authors.lastname: Gyenes
authors.affiliation: Maple Leaf Clinic, Toronto, Ontario, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada ; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.affiliation: Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada ; Department of Immunology, University of Toronto, Toronto, Ontario, Canada ; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016753:Interleukin-10