title: CD8(low)CD28(-) T Cells: A Human CD8 T-Suppressor Subpopulation With Alloantigen Specificity Induced by Soluble HLA-A2 Dimer In Vitro.
abstract: CD8(+) suppressor T cells have been demonstrated to provide protection of allografts from rejection. We previously reported that soluble peptide/HLA-A2 dimer shows peptide-specific inhibitory effects on alloresponse in a coculture of peptide-pulsed T2 cells with HLA-A2 negative lymphocytes in vitro. Here we found a subset of CD8(low)CD28(-) T cells that was induced in the dimer-treated coculture. Importantly, this population showed hyporesponsiveness to the alloantigen restimulation as well as alloantigen-specific suppression on alloreactive T cells in a cell-cell contact-dependent fashion. The suppressive mechanisms of CD8(low)CD28(-) T cells involved an elevated expression of membrane-bound TGF-β1, but not Foxp3, CTLA-4, or IL-10. Furthermore, an overrepresention of CD8(low)CD28(-) T cells was observed in the patients after allogeneic platelet transfusion and positively correlated with the elevated concentrations of plasma HLA class I antigens. Our findings demonstrated that soluble HLA-A2 dimer could efficiently induce the tolerant CD8(low)CD28(-) T cells with alloantigen-specific suppression on alloreactive T cells. This study might provide a new strategy for preparation of donor-specific suppressor T cells and represent an attractive alternative for induction of allograft tolerance.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lichen
authors.initials: L
authors.lastname: Ouyang
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.forename: Victor Tunje
authors.initials: VT
authors.lastname: Jeza
authors.forename: Yeli
authors.initials: Y
authors.lastname: Gong
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
authors.forename: Xiufang
authors.initials: X
authors.lastname: Weng
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D018106:CD28 Antigens; D015789:HLA-A2 Antigen; D007519:Isoantigens