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EnglishIn mice, activation of the Notch pathway in T cells by antigen-presenting cells overexpressing Notch ligands favors differentiation of regulatory T lymphocytes responsible for antigen-specific tolerance. To determine whether this mechanism operates in human T cells, we used Epstein-Barr virus-positive lymphoblastoid cell lines (EBV-LCL) as our (viral) antigen-presenting cells and overexpressed the Notch ligand Jagged-1 (EBV-LCL J1) by adenoviral transduction. The EBV-LCL J1s were cocultured with autologous T cells, and the proliferative and cytotoxic responses to EBV antigens were measured. Transduction had no effect on EBV-LCL expression of major histocompatibility complex (MHC) antigens or of costimulatory molecules CD80, CD86, and CD40. However, we observed a 35% inhibition of proliferation and a >65% reduction in cytotoxic-T-cell activity, and interleukin 10 production was increased ninefold. These EBV-LCL J1-stimulated T lymphocytes act as antigen-specific regulatory cells, since their addition to fresh autologous T cells cultured with autologous nontransduced EBV-LCL cells significantly inhibited both proliferation and cytotoxic effector function. Within the inhibitory population, CD4(+)CD25(+) and CD8(+)CD25(-) T cells had the greatest activity. This inhibition appears to be antigen-specific, since responses to Candida and cytomegalovirus antigens were unaffected. Hence, transgenic expression of Jagged-1 by antigen-presenting cells can induce antigen-specific regulatory T cells in humans and modify immune responses to viral antigens
Vigouroux, S., Yvon, E., Wagner, H., Biagi, E., Dotti, G., Sili, U., et al. (2003). Induction of antigen-specific regulatory T cells following overexpression of a Notch ligand by human B lymphocytes. JOURNAL OF VIROLOGY, 77(20), 10872-10880 [10.1128/JVI.77.20.10872-10880.2003].
| Citazione: | Vigouroux, S., Yvon, E., Wagner, H., Biagi, E., Dotti, G., Sili, U., et al. (2003). Induction of antigen-specific regulatory T cells following overexpression of a Notch ligand by human B lymphocytes. JOURNAL OF VIROLOGY, 77(20), 10872-10880 [10.1128/JVI.77.20.10872-10880.2003]. | |
| Tipo: | Articolo in rivista - Articolo scientifico | |
| Carattere della pubblicazione: | Scientifica | |
| Titolo: | Induction of antigen-specific regulatory T cells following overexpression of a Notch ligand by human B lymphocytes | |
| Autori: | Vigouroux, S; Yvon, E; Wagner, H; Biagi, E; Dotti, G; Sili, U; Lira, C; Rooney, C; Brenner, M | |
| Autori: | ||
| Data di pubblicazione: | ott-2003 | |
| Lingua: | English | |
| Rivista: | JOURNAL OF VIROLOGY | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1128/JVI.77.20.10872-10880.2003 | |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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