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Titolo:
Interleukin-12 differentially regulates expression of IFN-gamma and interleukin-2 in human T lymphoblasts
Autore:
Dickensheets, HL; Freeman, SL; Donnelly, RP;
Indirizzi:
US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USAUS FDA Rockville MD USA 20852 Div Cytokine Biol, Rockville, MD 20852 USA
Titolo Testata:
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
fascicolo: 10, volume: 20, anno: 2000,
pagine: 897 - 905
SICI:
1079-9907(200010)20:10<897:IDREOI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; HUMAN MONOCYTES; TYROSINE PHOSPHORYLATION; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; IL-12 RECEPTOR; HUMAN-LYMPHOCYTES; TH1 CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Donnelly, RP US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-538,1401 Rockville Pike, Rockville, MD 20852 USA US FDA HFM-538,1401 Rockville Pike Rockville MD USA 20852 USA
Citazione:
H.L. Dickensheets et al., "Interleukin-12 differentially regulates expression of IFN-gamma and interleukin-2 in human T lymphoblasts", J INTERF CY, 20(10), 2000, pp. 897-905

Abstract

Interleukin-12 (IL-12) is known to upregulate expression of interferon-gamma (IFN-gamma) by activated T cells. However, the effects of IL-12 on production of other Th1-type cytokines are less well defined. In this study, we examined the effects of IL-12 on expression of several cytokines, includingIFN-gamma, IL-2, tumor necrosis factor-a (TNF-alpha), and IL-10, by primary human CD3(+) T cells. Although purified resting T cells were largely nonresponsive to IL-12 stimulation, anti-CD3-activated T cell blasts were strongly responsive, as demonstrated by the ability of IL-12 to induce Stat4 DNA-binding activity. Restimulation of T lymphoblasts on immobilized anti-CD3 monoclonal antibodies (mAb) induced rapid expression of TNF-alpha mRNA and more gradual increases in mRNA levels for IL-2, IFN-gamma, and IL-10. IL-12markedly upregulated expression of IFN-gamma and IL-10 but downregulated expression of IL-2 in a dose-dependent and time-dependent manner. The levelsof IL-2 produced by IL-12-treated T cells correlated inversely with the levels of IL-10. Moreover, neutralization of IL-10 activity with anti-IL-10 antibodies normalized IL-2 production by IL-12-treated T cells, confirming that the inhibition of IL-2 production by IL-12 was IL-10 mediated. Thus, IL-12 amplified expression of IFN-gamma and IL-10 and, via its ability to upregulate production of IL-10, inhibited expression of IL-2. These findings demonstrate that IL-12 differentially regulates expression of the Th1-type lymphokines, IFN-gamma and IL-2, in T lymphoblasts.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 08:13:25