Polyclonally Derived Alloantigen-Specific T Regulatory Cells Exhibit Target-Specific Suppression and Capture MHC Class II from Dendritic Cells.

Autor:	Oya Y; Laboratory of Autoimmune Diseases, Department of Clinical Research, National Hospital Organization Chibahigashi National Hospital, Chiba City, Chiba, Japan.; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Department of Rheumatology, Allergy and Clinical Immunology, National Hospital Organization Chibahigashi National Hospital, Chiba City, Chiba, Japan., Tanaka Y; Laboratory of Autoimmune Diseases, Department of Clinical Research, National Hospital Organization Chibahigashi National Hospital, Chiba City, Chiba, Japan., Nakazawa T; Department of Rheumatology, Allergy and Clinical Immunology, National Hospital Organization Chibahigashi National Hospital, Chiba City, Chiba, Japan., Matsumura R; Department of Rheumatology, Allergy and Clinical Immunology, National Hospital Organization Chibahigashi National Hospital, Chiba City, Chiba, Japan., Glass DD; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Nakajima H; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University Hospital, Chiba City, Chiba, Japan., Shevach EM; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Jun 15; Vol. 212 (12), pp. 1891-1903.
DOI:	10.4049/jimmunol.2300780
Abstrakt:	Foxp3+ T regulatory (Treg) cells prevent allograft rejection and graft-versus-host disease. Although polyclonal Tregs have been used both in animal models and in humans, the fine specificity of their suppressive function is poorly defined. We have generated mouse recipient-derived alloantigen-specific Tregs in vitro and explored the fine specificity of their suppressive function and their mechanism of action in vitro and in vivo. In vitro, when alloantigen and peptide Ag were both presented on the same dendritic cell, both responses were suppressed by iTregs specific either for the alloantigen or for the peptide Ag. In vivo, iTreg suppression was limited to the cognate Ag, and no bystander suppression was observed when both allo-antigen and peptide Ag were present on the same dendritic cell. In vitro, alloantigen-specific Tregs captured cognate MHC but failed to capture noncognate MHC. Our results demonstrate that a polyclonal population of iTregs generated from naive T cells can mediate highly specific function in vivo and support the view that Treg therapy, even with unselected polyclonal populations, is likely to be target antigen-specific and that bystander responses to self-antigens or to infectious agents are unlikely. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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