BACKGROUND: The novel immunosuppressive molecule, CD200, has been reported to induce immunoregulation after interaction with its receptor(s), CD200R(s), in part at least through augmented induction of regulatory T-cell populations. Independent studies have also described increased expression of indoleamine-2,3-dioxygenase after CD200R triggering, whereas others have provided evidence that TGF-beta is important for the induction or function of many populations of regulatory T cells. We have asked whether a hybrid molecule in which a soluble fusion protein containing CD200, CD200Fc, was linked to TGF-beta through a glycine linker (Gly6) functions as a superior immunosuppressant molecule when compared with CD200Fc or TGF-beta alone, or in combination. METHODS: The hybrid molecule CD200FcGly6TGF-beta was expressed by transient transfection in CHO cells and purified over a protein A column. Functional activity of this and recombinant CD200Fc or TGF-beta alone were assessed in mixed leukocyte cultures (MLCs) and in skin graft rejection in vivo. RESULTS: Immunosuppression mediated by CD200FcGly6TGF-beta is dependent on both functional CD200 and TGF-beta moieties, as indicated by inhibition of suppression using anti-CD200 or anti-TGF-beta antibodies. Using as responder cells, using antigen-presenting cell from mice with a deletion of the CD200R gene and responder T cells from mice with siRNA-mediated suppression of expression of the TGF-betaII receptor, we show that suppression follows binding to TGF-betaRII on T cells, and CD200R1 on antigen-presenting cells. Indoleamine-2,3-dioxygenase inhibitors did not attenuate suppression by CD200FcGly6TGF-beta. CONCLUSION: CD200FcGly6TGF-beta is a potent immunosuppressant in vivo and in vitro.
BACKGROUND: The novel immunosuppressive molecule, CD200, has been reported to induce immunoregulation after interaction with its receptor(s), CD200R(s), in part at least through augmented induction of regulatory T-cell populations. Independent studies have also described increased expression of indoleamine-2,3-dioxygenase after CD200R triggering, whereas others have provided evidence that TGF-beta is important for the induction or function of many populations of regulatory T cells. We have asked whether a hybrid molecule in which a soluble fusion protein containing CD200, CD200Fc, was linked to TGF-beta through a glycine linker (Gly6) functions as a superior immunosuppressant molecule when compared with CD200Fc or TGF-beta alone, or in combination. METHODS: The hybrid molecule CD200FcGly6TGF-beta was expressed by transient transfection in CHO cells and purified over a protein A column. Functional activity of this and recombinant CD200Fc or TGF-beta alone were assessed in mixed leukocyte cultures (MLCs) and in skin graft rejection in vivo. RESULTS: Immunosuppression mediated by CD200FcGly6TGF-beta is dependent on both functional CD200 and TGF-beta moieties, as indicated by inhibition of suppression using anti-CD200 or anti-TGF-beta antibodies. Using as responder cells, using antigen-presenting cell from mice with a deletion of the CD200R gene and responder T cells from mice with siRNA-mediated suppression of expression of the TGF-betaII receptor, we show that suppression follows binding to TGF-betaRII on T cells, and CD200R1 on antigen-presenting cells. Indoleamine-2,3-dioxygenase inhibitors did not attenuate suppression by CD200FcGly6TGF-beta. CONCLUSION: CD200FcGly6TGF-beta is a potent immunosuppressant in vivo and in vitro.
Authors: Florbela A Vieira; Silvia F Gregório; Serena Ferraresso; Michael A S Thorne; Rita Costa; Massimo Milan; Luca Bargelloni; Melody S Clark; Adelino V M Canario; Deborah M Power Journal: BMC Genomics Date: 2011-10-07 Impact factor: 3.969
Authors: Alessandra Romano; Concetta Conticello; Maide Cavalli; Calogero Vetro; Alessia La Fauci; Nunziatina Laura Parrinello; Francesco Di Raimondo Journal: Biomed Res Int Date: 2014-06-11 Impact factor: 3.411
Authors: Christopher Paluch; Ana Mafalda Santos; Consuelo Anzilotti; Richard J Cornall; Simon J Davis Journal: Front Immunol Date: 2018-10-08 Impact factor: 7.561