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Effect of infusion of monoclonal antibodies to tumour necrosis factor‐receptor super family 25 on graft rejection in allo‐immune mice receiving autologous marrow transplantation
Author(s) -
Gorczynski Reginald M.,
Sadozai Hassan,
Zhu Fang,
Khatri Ismat
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12693
Subject(s) - monoclonal antibody , immunology , bone marrow , cyclophosphamide , medicine , transplantation , antigen , antibody , immune system , peripheral blood mononuclear cell , mixed lymphocyte reaction , biology , t cell , chemotherapy , in vitro , biochemistry
Summary Significant barriers to transplantation exist for individuals who are pre‐sensitized to donor antigen and have high titres of donor‐reactive antibody. We report the effect of autologous bone marrow transplantation ( BMT x) after myeloablation in pre‐sensitized mice along with the use of monoclonal antibodies ( mA bs) to tumour necrosis factor‐receptor super family 25 ( TNFRSF 25), expressed on regulatory T (Treg) cells. C57 BL /6 mice, which had been sensitized earlier with BALB /c skin allografts, received secondary BALB /c grafts after the primary grafts had been rejected. Subsequently, recipient mice underwent myeloablation with cyclophosphamide and busulphan and were injected with T‐cell‐depleted bone marrow from CD 45.1 congenic donors ( BMT x). Recipient mice underwent immunosuppressive treatment with rapamycin. A subgroup of mice was also treated with mA bs to TNFRSF 25. Control mice were pre‐sensitized mice that received cyclophosphamide and busulphan followed by rapamycin. BMT x‐treated mice had significantly prolonged skin graft survival versus control mice. These mice also showed attenuated donor‐specific mixed lymphocyte co‐culture responses relative to controls, increased splenic Treg cells and markedly diminished serum anti‐donor IgG. Infusion of anti‐ TNFRSF 25 mA bs further augmented graft survival and increased graft‐infiltrating Treg cells. These mA bs also expanded murine and human Treg cells in vitro with the capacity to attenuate mixed lymphocyte co‐cultures using fresh peripheral blood mononuclear cells. Overall, this study delineates the roles of autologous BMT x and anti‐ TNFRSF 25 mA bs in expanding Treg cells and attenuating alloimmune responses in pre‐sensitized mice.