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*
Roche Milano Ricerche, Milan, Italy; and
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche, Inc., Nutley, NJ 07110
Type I IFNs (IFN-
/ß), in addition to IL-12, have been shown to
play an important role in the differentiation of human, but not mouse,
Th cells. We show here that IFN-/ß act directly on human T cells
to drive Th1 development, bypassing the need for IL-12-induced
signaling, whereas IFN- cannot substitute IL-12 for mouse Th1
development. The molecular basis for this species specificity is that
IFN-/ß activate Stat4 in differentiating human, but not mouse, Th
cells. Unlike IL-12, which acts only on Th1 cells, IFN-/ß can
activate Stat4 not only in human Th1, but also in Th2 cells. However,
restimulation of human Th2 lines and clones in the presence of IFN-
does not induce the production of IFN-
. These results suggest that
activation of Stat4, which is necessary for the differentiation of
naive T cells into polarized Th1 cells, is not sufficient to induce
phenotype reversal of human Th2 cells.
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V. L. Heath, L. Showe, C. Crain, F. J. Barrat, G. Trinchieri, and A. O'Garra Cutting Edge: Ectopic Expression of the IL-12 Receptor-{beta}2 in Developing and Committed Th2 Cells Does Not Affect the Production of IL-4 or Induce the Production of IFN-{gamma} J. Immunol., March 15, 2000; 164(6): 2861 - 2865. [Abstract] [Full Text] [PDF]
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J. D. Farrar, J. D. Smith, T. L. Murphy, and K. M. Murphy Recruitment of Stat4 to the Human Interferon-alpha /beta Receptor Requires Activated Stat2 J. Biol. Chem., January 28, 2000; 275(4): 2693 - 2697. [Abstract] [Full Text] [PDF]
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H. Vallin, A. Perers, G. V. Alm, and L. Ronnblom Anti-Double-Stranded DNA Antibodies and Immunostimulatory Plasmid DNA in Combination Mimic the Endogenous IFN-{alpha} Inducer in Systemic Lupus Erythematosus J. Immunol., December 1, 1999; 163(11): 6306 - 6313. [Abstract] [Full Text] [PDF]
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L. Colantonio, A. Iellem, B. Clissi, R. Pardi, L. Rogge, F. Sinigaglia, and D. D'Ambrosio Upregulation of Integrin alpha 6/beta 1 and Chemokine Receptor CCR1 by Interleukin-12 Promotes the Migration of Human Type 1 Helper T Cells Blood, November 1, 1999; 94(9): 2981 - 2989. [Abstract] [Full Text] [PDF]
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C. A. v. Wely, P. C. L. Beverley, S. J. Brett, C. J. Britten, and J. P. Tite Expression of L-Selectin on Th1 Cells Is Regulated by IL-12 J. Immunol., August 1, 1999; 163(3): 1214 - 1221. [Abstract] [Full Text] [PDF]
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L. Rogge, A. Papi, D. H. Presky, M. Biffi, L. J. Minetti, D. Miotto, C. Agostini, G. Semenzato, L. M. Fabbri, and F. Sinigaglia Antibodies to the IL-12 Receptor {beta}2 Chain Mark Human Th1 But Not Th2 Cells In Vitro and In Vivo J. Immunol., April 1, 1999; 162(7): 3926 - 3932. [Abstract] [Full Text] [PDF]
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E. M. Coccia, N. Passini, A. Battistini, C. Pini, F. Sinigaglia, and L. Rogge Interleukin-12 Induces Expression of Interferon Regulatory Factor-1 via Signal Transducer and Activator of Transcription-4 in Human T Helper Type 1 Cells J. Biol. Chem., March 5, 1999; 274(10): 6698 - 6703. [Abstract] [Full Text] [PDF]
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M. C. Braun, J. He, C.-Y. Wu, and B. L. Kelsall Cholera Toxin Suppresses Interleukin (IL)-12 Production and IL-12 Receptor {beta}1 and {beta}2 Chain Expression J. Exp. Med., February 1, 1999; 189(3): 541 - 552. [Abstract] [Full Text] [PDF]
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