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Titolo:
CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade
Autore:
Taylor, PA; Noelle, RJ; Blazar, BR;
Indirizzi:
Univ Minnesota, Ctr Canc, Dept Pediat, BMT Div, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 MT Div, Minneapolis, MN 55455 USA Dartmouth Med Coll, Dept Microbiol, Lebanon, NH 03756 USA Dartmouth Med Coll Lebanon NH USA 03756 Microbiol, Lebanon, NH 03756 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 11, volume: 193, anno: 2001,
pagine: 1311 - 1317
SICI:
0022-1007(20010604)193:11<1311:CIRCAR>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTE-ASSOCIATED ANTIGEN-4; RENAL-ALLOGRAFT REJECTION; IMMUNOREGULATORY T-CELLS; ANTI-CD40 LIGAND; AUTOIMMUNE-DISEASE; EFFECTOR FUNCTION; EX-VIVO; ANTIBODY; DONOR; HYPORESPONSIVENESS;
Keywords:
regulatory T cell; IL-2 receptor alpha chain (CD25); tolerance; transplantation; in vivo animal models;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Blazar, BR Univ Minnesota, Ctr Canc, Dept Pediat, BMT Div, MMC 109,420 SE Delaware St, Minneapolis, MN 55455 USA Univ Minnesota MMC 109,420 SE Delaware St Minneapolis MN USA 55455
Citazione:
P.A. Taylor et al., "CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade", J EXP MED, 193(11), 2001, pp. 1311-1317

Abstract

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)/CD40or 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 vitroand 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.

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Documento generato il 07/04/20 alle ore 21:16:37