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Titolo:
CTLA-4 up-regulation plays a role in tolerance mediated by CD45
Autore:
Fecteau, S; Basadonna, GP; Freitas, A; Ariyan, C; Sayegh, MH; Rothstein, DM;
Indirizzi:
Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 pt Internal Med, New Haven, CT 06520 USA Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 Med, Dept Surg, New Haven, CT 06520 USA Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ens Hosp, Dept Med, Boston, MA 02115 USA
Titolo Testata:
NATURE IMMUNOLOGY
fascicolo: 1, volume: 2, anno: 2001,
pagine: 58 - 63
SICI:
1529-2908(200101)2:1<58:CUPARI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE-PHOSPHATASE; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; T-CELL ACTIVATION; IN-VIVO; INTERLEUKIN-2 SECRETION; NEGATIVE REGULATOR; DISTINCT ISOFORMS; EXPRESSION; INDUCTION; ANTIBODY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Rothstein, DM Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA Yale Univ 333 Cedar St New Haven CT USA 06520 , CT 06520 USA
Citazione:
S. Fecteau et al., "CTLA-4 up-regulation plays a role in tolerance mediated by CD45", NAT IMMUNOL, 2(1), 2001, pp. 58-63

Abstract

Cytolytic T lymphocyte-associated antigen 4 (CTLA-4) is a critical down-regulatory molecule in T cells that plays a major role in peripheral tolerance. Although the CD45 protein tyrosine phosphatase is a potent immunomodulatory target, the mechanisms by which antibody against CD45RB isoforms (anti-CD45RB) induces allograft tolerance remain unclear. We show here that anti-CD45RB treatment alters CD45 isoform expression on T cells, which is associated with rapid up-regulation of CTLA-4 expression. These effects appear specific and occur without up-regulation of other activation markers. Administration of a blocking monoclonal antibody to CTLA-4 at the time of transplantation prevents anti CD45RB therapy from prolonging islet allograft survival. In addition, treatment with cyclosporin A blocks anti-CD45RB-induced CTLA-4 expression and promotes acute rejection. These data suggest that anti-CD45RB acts through mechanisms that include CTLA-4 up-regulation and demonstrate a link between CD45 and CTLA-4 that depends on calcineurin-mediated signaling. They demonstrate also that CTLA-4 expression may be specifically targeted to enhance allograft acceptance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 14:15:12