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Titolo:
LACK OF IL-12 SIGNALING IN HUMAN ALLERGEN-SPECIFIC TH2 CELLS
Autore:
HILKENS CMU; MESSER G; TESSELAAR K; VANRIETSCHOTEN AGI; KAPSENBERG ML; WIERENGA EA;
Indirizzi:
UNIV AMSTERDAM,ACAD MED CTR,DEPT HISTOL & CELL BIOL,MEIBERGDREEF 15 NL-1105 AZ AMSTERDAM NETHERLANDS NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT CLIN VIROL AMSTERDAM NETHERLANDS UNIV MUNICH,DEPT DERMATOL D-8000 MUNICH GERMANY
Titolo Testata:
The Journal of immunology
fascicolo: 10, volume: 157, anno: 1996,
pagine: 4316 - 4321
SICI:
0022-1767(1996)157:10<4316:LOISIH>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HELPER TYPE-1 TH1; CD4+ T-CELLS; TYROSINE PHOSPHORYLATION; IFN-GAMMA; MONOCLONAL-ANTIBODIES; FUNCTIONAL SUBSETS; LYMPHOCYTES-T; INTERLEUKIN-12; CLONES; INTERFERON;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
C.M.U. Hilkens et al., "LACK OF IL-12 SIGNALING IN HUMAN ALLERGEN-SPECIFIC TH2 CELLS", The Journal of immunology, 157(10), 1996, pp. 4316-4321

Abstract

IL-12 is a powerful skewer of CD4(+) T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells, In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells, To this aim, allergen-specific CD4(+) Tcell clones (TCC) were generated from the peripheral blood of three atopic patients, and their cytokine profiles were analyzed, The majority of these TCC exhibited a strongly polarized Th2 cytokine profile, and the production of IFN-gamma could not be induced by exogenous IL-12,Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production, The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12-induced phosphorylation of STAT4 (signal transducerand activator of transcription-4), a transcription factor that is typically involved in IL-12 signaling, Consequently, IL-12 also failed toinduce the DNA-binding activity of STAT4-containing complexes in the nuclei of these Th2 clones, All TCC expressed equal levels of the low-affinity IL-12R beta 1 subunit. Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and, therefore, cannot be induced to produce IFN-gamma. The apparent high frequency of IL-12-nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses, but only affecting newly recruited naive Th cells.

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Documento generato il 21/09/20 alle ore 19:17:17