Isolation and characterization of human antigen-specific TCR alpha beta(+) CD4(-)CD8(-) double-negative regulatory T cells

Fischer, K. and Voelkl, S. and Heymann, J. and Przybylski, G. K. and Mondal, K. and Laumer, M. and Kunz-Schughart, Leoni and Schmidt, CA and Andreesen, Reinhard and Mackensen, Andreas (2005) Isolation and characterization of human antigen-specific TCR alpha beta(+) CD4(-)CD8(-) double-negative regulatory T cells. BLOOD, 105 (7). pp. 2828-2835. ISSN 0006-4971, 1528-0020

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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.

Item Type: Article
Uncontrolled Keywords: VERSUS-HOST-DISEASE; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; RECEPTOR ALPHA-CHAINS; IN-VITRO; PERIPHERAL-BLOOD; HELPER CELLS; 2 SUBSETS; TOLERANCE; MEMORY; DIFFERENTIATION;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 17 May 2021 07:37
Last Modified: 17 May 2021 07:37
URI: https://pred.uni-regensburg.de/id/eprint/36282

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