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Titolo:
Comparison of Fas- versus perforin-mediated pathways of cytotoxicity in TCR- and Thy-1-activated murine T cells
Autore:
Kojima, H; Toda, M; Sitkovsky, MV;
Indirizzi:
NIAID, Biochem & Immunopharmacol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA NIAID Bethesda MD USA 20892 ect, Immunol Lab, NIH, Bethesda, MD 20892 USA Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan Keio Univ Tokyo Japan 1608582 ch Med, Dept Physiol, Tokyo 1608582, Japan
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 3, volume: 12, anno: 2000,
pagine: 365 - 374
SICI:
0953-8178(200003)12:3<365:COFVPP>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; LYMPHOKINE PRODUCTION; CANCER-IMMUNOTHERAPY; SIGNAL-TRANSDUCTION; RECEPTOR COMPLEX; CO-EXPRESSION; MICE LACKING; ACTIVATION; THY-1;
Keywords:
cytotoxic T lymphocyte; Fas ligand; perforin; retargeting; TCR; Thy-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Sitkovsky, MV NIAID, Biochem & Immunopharmacol Sect, Immunol Lab, NIH, Bldg 10-11N311,10Ctr Dr,MSC 1892, Bethesda, MD 20892 USA NIAID Bldg 10-11N311,10 Ctr Dr,MSC 1892 Bethesda MD USA 20892
Citazione:
H. Kojima et al., "Comparison of Fas- versus perforin-mediated pathways of cytotoxicity in TCR- and Thy-1-activated murine T cells", INT IMMUNOL, 12(3), 2000, pp. 365-374

Abstract

T cell-mediated cytotoxicity can be triggered by cross-linking of TCR or Thy-1 surface proteins. While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it was not clear which mechanism was utilized by Thy-1-triggered signals and which pathway of cytotoxicity was triggered at low levels of antigen expression. It is shown that glycophosphatidylinositol-linked surface glycoprotein Thy-1 preferentially activates FasL-Fas- but not perforin-mediated cytotoxicity. This is explained by the lesser intensity of Thy-1-mediated signaling in T cells. The data suggest that Thy-1-triggered Fas-mediated cytotoxicityis completely dependent on cross-talk between Thy-1 and Ton signals since mutations in TCR-CD3 complex molecules or inhibition of tyrosine kinases orcalcineurin abolished or strongly inhibited Thy-1-triggered FasL-Fas-mediated cytotoxicity. Lower concentrations of antigenic peptide or levels of cross-linking with anti-TCR-CDS mAb are required to trigger Fas-mediated thanperforin-mediated cytotoxicity by different cytotoxic T lymphocyte (CTL) lines and clones, and it is shown that cross-linking of Thy-1 is much less efficient in triggering accumulation of second messengers (intracellular Ca2) than cross-linking of TCR on CTL. Taken together, these data reflect thepossibility of differential activation of FasL and/or perforin pathways ofcytotoxicity depending on the nature of activating stimuli and surface receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:32:42