An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.

Zhao G, Moore DJ, Lee KM, Kim JI, Duff PE, O'Connor MR, Hirohashi T, Lei J, Yang M, Markmann JF, Deng S
Am J Transplant. 2010 10 (4): 796-801

PMID: 20199511 · PMCID: PMC2934759 · DOI:10.1111/j.1600-6143.2010.03027.x

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.

MeSH Terms (10)

Adaptive Immunity Animals B-Lymphocytes Graft Survival Interleukin-10 Mice Mice, Inbred C3H Mice, Inbred C57BL Neutralization Tests Transplantation Immunology

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