Gattinoni, Luca;
Ranganathan, Anju;
Surman, Deborah R.;
Palmer, Douglas C.;
Antony, Paul A.;
Theoret, Marc R.;
Heimann, David M.;
Rosenberg, Steven A.;
Restifo, Nicholas P.
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent
Beteiligte:
Gattinoni, Luca;
Ranganathan, Anju;
Surman, Deborah R.;
Palmer, Douglas C.;
Antony, Paul A.;
Theoret, Marc R.;
Heimann, David M.;
Rosenberg, Steven A.;
Restifo, Nicholas P.
Erschienen:
American Society of Hematology, 2006
Erschienen in:Blood
Sprache:
Englisch
DOI:
10.1182/blood-2006-07-034066
ISSN:
0006-4971;
1528-0020
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) maintains peripheral tolerance by suppressing T-cell activation and proliferation but its precise role in vivo remains unclear. We sought to elucidate the impact of CTLA-4 expression on self/tumor-reactive CD8+ T cells by using the glycoprotein (gp) 100–specific T-cell receptor (TCR) transgenic mouse, pmel-1. pmel-1 CLTA-4–/– mice developed profound, accelerated autoimmune vitiligo. This enhanced autoimmunity was associated with a small but highly activated CD8+ T-cell population and large numbers of CD4+ T cells not expressing the transgenic TCR. Adoptive transfer of pmel-1 CLTA-4–/– CD8+ T cells did not mediate superior antitumor immunity in the settings of either large established tumors or tumor challenge, suggesting that the mere absence of CTLA-4–mediated inhibition on CD8+ T cells did not directly promote enhancement of their effector functions. Removal of CD4+ T cells by crossing the pmel-1 CLTA-4–/– mouse onto a Rag-1–/– background resulted in the complete abrogation of CD8+ T-cell activation and autoimmune manifestations. The effects of CD4+ CLTA-4–/– T cells were dependent on the absence of CTLA-4 on CD8+ T cells. These results indicated that CD8+ CLTA-4–/– T-cell–mediated autoimmunity and tumor immunity required CD4+ T cells in which the function was dysregulated by the absence of CTLA-4–mediated negative costimulation.</jats:p>