title: B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation.
abstract: Alloreactive memory T cells mediate accelerated allograft rejection and transplant tolerance resistance. Recent studies have shown that B cell deficient-μMT mice fail to mount donor-specific memory T cell responses after transplantation. At the same time, other studies showed that pretransplant B cell depletion using rituximab (IgG1 anti-CD20 mAb) combined with cyclosporine A promoted the survival of islet allografts in monkeys. In this study, we investigated the effect of anti-CD20 antibody-mediated B cell depletion on the memory T cell alloresponse in mice. Wild-type and anti-OVA TCR transgenic mice were treated with an IgG2a anti-CD20 monoclonal antibody, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs but spared some B cells in the bone marrow. B cell depletion did not affect the direct alloresponse but resulted in a marked increase of indirect alloresponse after skin transplantation of naïve mice. Furthermore, in allosensitized mice, anti-CD20 mAb treatment enhanced the reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti-CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered.
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Marino
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: J T
authors.initials: JT
authors.lastname: Paster
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Trowell
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Maxwell
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: K H
authors.initials: KH
authors.lastname: Briggs
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: P
authors.initials: P
authors.lastname: Crosby Bertorini
authors.affiliation: Center for Transplant Sciences, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: G
authors.initials: G
authors.lastname: Benichou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016038:Skin Transplantation; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007518:Isoantibodies
keywords: T cell biology; alloantigen; basic (laboratory) research/science; immunobiology; lymphocyte biology: activation; major histocompatibility complex (MHC)