The Journal of Experimental Medicine
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Published 21 June 2004. doi:10.1084/jem.20032014
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 12, 1619-1630
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Interferon {gamma} Enhances Both In Vitro and In Vivo Priming of CD4+ T Cells for IL-4 Production

Petr Bocek, Jr.1, Gilles Foucras1,2, and William E. Paul1

1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
2 National Veterinary School, Pathogen-Host Interactions, UMR INRA/ENVT 1225, 31076 Toulouse, Cedex 03, France

Address correspondence to Petr Bocek, Jr., at his present address Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6610 Rockledge Dr., Rm. 3060, Bethesda, MD 20892. Phone: (301) 451-3104; Fax: (301) 402-0175; email: pbocek{at}niaid.nih.gov

Classical studies have demonstrated that in vitro priming of naive CD4 T cells to become T helper (Th)2 cells is strikingly dependent on interleukin (IL)-4, whereas priming for interferon (IFN){gamma} production is IL-12/IFN{gamma}-dependent. Therefore, it was quite surprising when we noted that priming of naive C57BL/6 CD4+ cells to become IL-4 producers was substantially inhibited by the addition of anti-IFN{gamma} antibodies. This was true using immobilized anti-CD3 and anti-CD28 antibodies or soluble anti-CD3/anti-CD28 and antigen-presenting cells in the presence or absence of added IL-4. Priming of CD4 T cells from IFN{gamma}–/– C57BL/6 mice with immobilized anti-CD3 and anti-CD28 resulted in limited production of IL-4, even with the addition of 1,000 U/ml of IL-4. Titrating IFN{gamma} into such cultures showed a striking increase in the proportion of T cells that secreted IL-4 upon challenge; this effect was completely IL-4–dependent in that it was blocked with anti–IL-4 antibody. Thus, IFN{gamma} plays an unanticipated but substantial role in Th2 priming, although it is an important Th1 cytokine, and under certain circumstances a Th1 inducer.

Key Words: T cell activation • cell differentiation • T lymphocyte subsets • cytokine • T-bet

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; STAT, signal transducer and activator of transcription.


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