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Titolo:
Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression:IL-12 and tumor necrosis factor-alpha synergize for IL-12R expression at low antigen dose
Autore:
Ahlers, JD; Belyakov, IM; Matsui, S; Berzofsky, JA;
Indirizzi:
NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 11, volume: 13, anno: 2001,
pagine: 1433 - 1442
SICI:
0953-8178(200111)13:11<1433:SDTTII>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALTERED PEPTIDE LIGANDS; PHENOTYPE DEVELOPMENT; TNF-ALPHA; TH2 CELLS; IFN-GAMMA; T-CELLS; CYTOKINE; DIFFERENTIATION; INTERLEUKIN-12; LYMPHOCYTES;
Keywords:
cellular activation; cytokine; cytokine receptors; T lymphocyte; T(h)1/T(h)2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Berzofsky, JA NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Sect, NIH, Bethesda, MD 20892 USA
Citazione:
J.D. Ahlers et al., "Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression:IL-12 and tumor necrosis factor-alpha synergize for IL-12R expression at low antigen dose", INT IMMUNOL, 13(11), 2001, pp. 1433-1442

Abstract

Regulation of the IL-12 receptor (IL-12R) beta2 chain has been suggested to function as a molecular switch in determining T cell phenotype. However, because most studies have been carried out under conditions in which cell proliferation was occurring, it has been difficult to distinguish between instructive and selective mechanisms in regulating this key receptor. Here, in the course of trying to understand the mechanism for synergy between IL-12 and TNF-alpha in up-regulating IFN-gamma production, we find that when the stimulus through the TCR is too weak to induce cell proliferation, which would be needed for selection, IL-12 and TNF-alpha synergize to up-regulatenot only IFN-gamma, but also the IL-12R beta2 chain, which triggers IFN-gamma production. Neither cytokine alone was sufficient. This observation held true both in the absence of antigen-presenting cells (APC), when the stimulus was anti-CD3 on plastic, and in the presence of APC presenting ovalbumin peptide to TCR-transgenic T cells. In contrast, when the TCR signal was stronger, no cytokines were necessary to up-regulate the IL-12R. Our results support the strength of signal model in instructing Th phenotype, and suggest both an instructive role and, later, through the production of IFN-gamma, a selective role, of this synergistic combination of cytokines in the preferential differentiation and expansion of TO cells.

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Documento generato il 06/04/20 alle ore 08:54:25