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Adoptively Transferable Tolerance Induced by CD45RB Monoclonal Antibody

London Health Sciences Centre, University Campus, John P. Robarts Research Institute and Departments of Medicine, Surgery, Pathology, and Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.

Correspondence to Dr. Andrew I. Lazarovits, London Health Sciences Centre, University Campus, Room 4TU46, Box 5339, 339 Windermere Road, London, Ontario, Canada N6A 5A5. E-mail: alazarov{at}julian.uwo.ca

Abstract. The phenomenon of rejection remains the most serious problem in transplantation. The ultimate goal in transplant immunology is to develop therapeutic strategies that lead to tolerance. It has been shown that two injections of a monoclonal antibody to CD45RB leads to indefinite acceptance of renal allografts in mice. Moreover, the CD45RB monoclonal antibody reverses acute rejection and still induces tolerance. The purpose of this study was to assess mechanisms that could underlie this therapeutic benefit. It was shown that splenic lymphocytes from tolerant animals augmented proliferation in allogeneic mixed lymphocyte reactions against donor alloantigens, and the serum of tolerant mice contained donor-specific antibodies, mainly of the IgG1 isotype, suggesting the presence of TH2 cytokines. Tolerance could not be broken by interleukin-2 infusion, but tolerance could be adoptively transferred by transfusion of tolerant mouse CD4⁺ splenic lymphocytes into naive allografted animals. These data suggest that an active immunoregulatory mechanism is partly responsible for the therapeutic effect. CD45RB-directed therapy may find clinical application in organ transplantation in human patients.

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