An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.
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.
Zhao
G
G
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.
Moore
D J
DJ
Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt Children's Hospital, Nashville, TN.
Lee
K M
KM
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Kim
J I
JI
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Duff
P E
PE
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
O'Connor
M R
MR
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Hirohashi
T
T
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Lei
J
J
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Yang
M
M
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.
Markmann
J F
JF
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Deng
S
S
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.
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
D016753:Interleukin-10