Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(-)CD8- double-negative regulatory T cells.
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.
Fischer
Karin
K
Department of Hematology and Oncology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
Voelkl
Simon
S
Heymann
Jana
J
Przybylski
Grzegorz K
GK
Mondal
Krishna
K
Laumer
Monika
M
Kunz-Schughart
Leoni
L
Schmidt
Christian A
CA
Andreesen
Reinhard
R
Mackensen
Andreas
A
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
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta