title: An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.
abstract: Monoclonal antibody against the CD45RB protein induces stable transplantation tolerance to multiple types of allograft. We have previously established that this tolerance protocol relies on the regulatory function of B lymphocytes for its effect. B lymphocytes have also been reported to participate in immune regulation in several other settings. In most of these systems, the regulatory function of B lymphocytes depends on the production of IL-10. Therefore, we investigated the role of IL-10 in the anti-CD45RB model of B-cell-mediated transplantation tolerance. Surprisingly, using antibody-mediated neutralization of IL-10, IL-10-deficient recipients and adoptive transfer of IL-10-deficient B lymphocytes, we found that IL-10 actually counter-regulates tolerance induced by anti-CD45RB. Furthermore, neutralization of IL-10 reduced the development of chronic allograft vasculopathy compared to anti-CD45RB alone and reduced the production of graft reactive alloantibodies. These data suggest that the participation of regulatory B lymphocytes in transplantation tolerance may be distinct from how they operate in other systems. Identifying the specific B lymphocytes that mediate transplantation tolerance and defining their mechanism of action may yield new insights into the complex cellular network through which antigen-specific tolerance is established and maintained.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.|Department of Surgery, Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt Children's Hospital, Nashville, TN.
authors.forename: D J
authors.initials: DJ
authors.lastname: Moore
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: P E
authors.initials: PE
authors.lastname: Duff
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: M R
authors.initials: MR
authors.lastname: O'Connor
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Hirohashi
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.|Department of Surgery, Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.|Department of Surgery, Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: S
authors.initials: S
authors.lastname: Deng
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006085:Graft Survival; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D014181:Transplantation Immunology
chemical_list: D016753:Interleukin-10