title: Specificity of CD4+CD25+ regulatory T cell function in alloimmunity.
abstract: CD4+CD25+ regulatory T cells (TRegs) are critical for the acquisition of peripheral allograft tolerance. However, it is unclear whether TRegs are capable of mediating alloantigen-specific suppressive effects and, hence, contributing to the specificity of the tolerant state. In the current report we have used the ABM TCR transgenic (Tg) system, a C57BL/6-derived strain in which CD4+ T cells directly recognize the allogeneic MHC-II molecule I-A(bm12), to assess the capacity of TRegs to mediate allospecific effects. In these mice, 5-6% of Tg CD4+ T cells exhibit conventional markers of the TReg phenotype. ABM TRegs are more effective than wild-type polyclonal TRegs at suppressing effector immune responses directed against I-A(bm12) alloantigen both in vitro and in vivo. In contrast, they are incapable of suppressing responses directed against third-party alloantigens unless these are expressed in the same allograft as I-A(bm12). Taken together, our results indicate that in transplantation, TReg function is dependent on TCR stimulation, providing definitive evidence for their specificity in the regulation of alloimmune responses.
authors.affiliation: Department of Medicine, Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Fueyo
authors.forename: Sigrid
authors.initials: S
authors.lastname: Sandner
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariat
authors.forename: James
authors.initials: J
authors.lastname: Kenny
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Sayegh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2