title: Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(-)CD8- double-negative regulatory T cells.
abstract: Down-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ags). Recently, a novel subset of Ag-specific T-cell receptor (TCR)alpha beta+ CD4(-)CD8- (double-negative [DN]) Treg cells has been found to be able to prevent the rejection of skin and heart allografts by specifically inhibiting the function of antigraft-specific CD8+ T cells. Here we demonstrate that peripheral DN Treg cells are present in humans, where they constitute about 1% of total CD3+ T cells, and consist of both naive and Ag-experienced cells. Similar to murine DN Treg cells, human DN Treg cells are able to acquire peptide-HLA-A2 complexes from antigen-presenting cells by cell contact-dependent mechanisms. Furthermore, such acquired peptide-HLA complexes appear to be functionally active, in that CD8+ T cells specific for the HLA-A2-restricted self-peptide, Melan-A, became sensitive to apoptosis by neighboring DN T cells after acquisition of Melan-A-HLA-A2 complexes and revealed a reduced proliferative response. These results demonstrate for the first time that a sizable population of peripheral DN Treg cells, which are able to suppress Ag-specific T cells, exists in humans. DN Treg cells may serve to limit clonal expansion of allo-Ag-specific T cells after transplantation.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Fischer
authors.forename: Simon
authors.initials: S
authors.lastname: Voelkl
authors.forename: Jana
authors.initials: J
authors.lastname: Heymann
authors.forename: Grzegorz K
authors.initials: GK
authors.lastname: Przybylski
authors.forename: Krishna
authors.initials: K
authors.lastname: Mondal
authors.forename: Monika
authors.initials: M
authors.lastname: Laumer
authors.forename: Leoni
authors.initials: L
authors.lastname: Kunz-Schughart
authors.forename: Christian A
authors.initials: CA
authors.lastname: Schmidt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta