Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro

Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103...

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Veröffentlicht in:Transplantation 2007-04, Vol.83 (8), p.1098-1106
Hauptverfasser: USS, Elena, YONG, Si-La, HOOIBRINK, Berend, VAN LIER, Rene A. W, TEN BERG, Ineke J. M
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container_end_page 1106
container_issue 8
container_start_page 1098
container_title Transplantation
container_volume 83
creator USS, Elena
YONG, Si-La
HOOIBRINK, Berend
VAN LIER, Rene A. W
TEN BERG, Ineke J. M
description Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103 directs T lymphocytes to their ligand E-cadherin, which is expressed on renal tubular epithelial cells, and CD103+ CD8+ T cells have been described to be present in late renal allograft rejection. We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC. Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity. Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. These data are relevant in the design of immunosuppressive drug regimens intended to induce and/or maintain transplantation tolerance.
doi_str_mv 10.1097/01.tp.0000259555.29762.f0
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Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity. Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. 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W</creatorcontrib><creatorcontrib>TEN BERG, Ineke J. M</creatorcontrib><title>Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103 directs T lymphocytes to their ligand E-cadherin, which is expressed on renal tubular epithelial cells, and CD103+ CD8+ T cells have been described to be present in late renal allograft rejection. We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC. 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subjects Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antigens, CD - immunology
Biological and medical sciences
Calcineurin - metabolism
Calcineurin Inhibitors
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - drug effects
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell Differentiation
Cell Proliferation
Cells, Cultured
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Integrin alpha Chains - immunology
Isoantigens - immunology
Medical sciences
Pharmacology. Drug treatments
Prednisolone - pharmacology
Sirolimus - pharmacology
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tissue, organ and graft immunology
title Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro
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