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An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.
Zhao, G; Moore, D J; Lee, K M; Kim, J I; Duff, P E; O'Connor, M R; Hirohashi, T; Lei, J; Yang, M; Markmann, J F; Deng, S.
Afiliação
  • Zhao G; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Moore DJ; Department of Surgery, Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
  • Lee KM; Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt Children's Hospital, Nashville, TN.
  • Kim JI; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Duff PE; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • O'Connor MR; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Hirohashi T; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Lei J; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Yang M; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Markmann JF; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Deng S; Department of Surgery, Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
Am J Transplant ; 10(4): 796-801, 2010 Apr.
Article em En | MEDLINE | ID: mdl-20199511
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Imunologia de Transplantes / Linfócitos B / Interleucina-10 / Imunidade Adaptativa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Marrocos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Imunologia de Transplantes / Linfócitos B / Interleucina-10 / Imunidade Adaptativa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Marrocos