Cd4+Cd25+ Immune Regulatory Cells Are Required for Induction of Tolerance to Alloantigen via Costimulatory Blockade
By P. Taylor, R. Noelle, B. Blazar. Journal of Experimental Medicine, 2001
623 citations recorded by the source corpus.
Immune regulatory CD4+CD25+ cells play a vital role in the induction and maintenance of self-tolerance and are essential for T cell homeostasis and the prevention of autoimmunity. Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. To determine whether CD4+CD25+ cells regulate T cell responses to alloantigen and are critical for tolerance induction, murine CD4+ T cells were tolerized to alloantigen via ex vivo CD40 ligand (CD40L)/CD40 or CD28/cytotoxic T lymphocyte–associated antigen 4/B7 blockade resulting in secondary mixed leukocyte reaction hyporesponsiveness and tolerance to alloantigen in vivo. CD4+CD25+ T cells were found to be potent regulators of alloresponses. Depletion of CD4+CD25+ T cells from the CD4+ responder population completely abrogated ex vivo tolerance induction to alloantigen as measured by intact responses to alloantigen restimulation in vitro and in vivo. Addback of CD4+CD25+ T cells to CD4+CD25− cultures restored tolerance induction. These data are the first to indicate that CD4+CD25+ cells are essential for the induction of tolerance to alloantigen and have important implications for tolerance-inducing strategies targeted at T cell costimulatory pathways.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/7c5526840be89643ee206e7f4ffe43d7a6e9505f
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Citations in the corpus
- CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses (2003, background): “Since the concept of regulatory cells was reawakened by the observations of several groups (1, 15, 19, 20), it has become evident that the intensity of many immune inflammatory reactions are subject to control by Treg.”
- Cutting Edge: Regulatory T Cells from Lung Cancer Patients Directly Inhibit Autologous T Cell Proliferation1 (2002, background): “Previous studies have shown that CD4 CD25 T cells prevent allograft rejection, both in vitro and in vivo (23, 24).”
- Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. (2004, background): “…have potent regulatory properties in both the induction and maintenance phases of in vivo tolerance to alloantigens in mice (Sakaguchi et al., 1995; Taylor et al., 2001; Cohen et al., 2002; Hoffmann et al., 2002) and humans (Beacher-Allan et al., 2001; Jonuleit et al., 2001; Levings et al., 2001;…”