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Titolo:
TRANSFORMING GROWTH-FACTOR-BETA INHIBITS IL-4 AND IFN-GAMMA PRODUCTION BY STIMULATED HUMAN T-CELLS
Autore:
HOLTER W; KALTHOFF FS; PICKL WF; EBNER C; MAJDIC O; KRAFT D; KNAPP W;
Indirizzi:
UNIV VIENNA,SFI,VIENNA INT RES COOPERAT CTR,INST IMMUNOL,BRUNNERSTR 59 A-1235 VIENNA AUSTRIA UNIV VIENNA,INST IMMUNOL A-1090 VIENNA AUSTRIA UNIV VIENNA,INST GEN & EXPTL PATHOL A-1090 VIENNA AUSTRIA SANDOZ GMBH A-1235 VIENNA AUSTRIA
Titolo Testata:
International immunology
fascicolo: 3, volume: 6, anno: 1994,
pagine: 469 - 475
SICI:
0953-8178(1994)6:3<469:TGIIAI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LYMPHOCYTES-T; CYTOKINE PRODUCTION; PROLIFERATION; SECRETION; RECEPTOR; INTERLEUKIN-4; EXPRESSION; MODULATION; ACTIVATION; PROTEIN;
Keywords:
CYTOKINE SYNTHESIS; T-CELLS; TRANSFORMING GROWTH FACTOR-BETA; TYROSINE PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
W. Holter et al., "TRANSFORMING GROWTH-FACTOR-BETA INHIBITS IL-4 AND IFN-GAMMA PRODUCTION BY STIMULATED HUMAN T-CELLS", International immunology, 6(3), 1994, pp. 469-475

Abstract

The present study investigates the effect of transforming growth factor (TGF)-beta on the production of IL-4 and IFN-gamma by the leukemia T(h)0 type cell line HUT78, by freshly isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-gamma, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-beta1. TGF-beta1 also reduced the accumulation of IL-4 and IFN-gamma specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-gamma production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-alpha or granulocyte macrophage colonystimulating factor had no effect. Because IL-2 is an important helpercytokine for the production of IL-4 and IFN-gamma, we investigated whether signal transduction through the IL-2 receptor is impaired by TGF-beta1. We found that tyrosine phosphorylation in response to IL-2 in HUT78 cells was strongly inhibited by a short preincubation with TGF-beta1. Evidence for an antagonistic role for TGF-beta1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-beta1 mediated inhibition of IL-4 and IFN-gamma production. Similar to its effect on HUT78 cells, TGF-beta1 also inhibited IL-4 and IFN-gammaproduction by freshly isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-gamma are both negatively controlled by TGF-beta under conditions where IL-2 production is unaffected by a mechanism which partially involves an inhibition of IL-2/IL-2R signal transduction. These data identify TGF-beta and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-gamma production.

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Documento generato il 30/10/20 alle ore 10:01:09