The Journal of Experimental Medicine
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Published online 2 October 2000.
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© The Rockefeller University Press, 0022-1007/2000/10/977/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 7, October 2, 2000 977-986

Original Article

Interferon {gamma} Signaling Alters the Function of T Helper Type 1 Cells

Gregory Z. Taua, Thierry von der Weide, Binfeng Lua, Simone Cowanb, Marina Kvatyukb, Alessandra Pernisb, Giorgio Cattorettid, Ned S. Braunsteinb, Robert L. Coffmane, and Paul B. Rothmanb,c
a Integrated Program in Cell, Molecular and Biophysical Studies, the
b Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032
c Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032
d Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032
e DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304

Correspondence to: Paul B. Rothman, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, P&S 8-425, Columbia University, 630 W. 168th St., New York, NY 10032. Tel:212-305-6982 Fax:212-305-1870

One mechanism regulating the ability of different subsets of T helper (Th) cells to respond to cytokines is the differential expression of cytokine receptors. For example, Th2 cells express both chains of the interferon {gamma} receptor (IFN-{gamma}R), whereas Th1 cells do not express the second chain of the IFN-{gamma}R (IFN-{gamma}R2) and are therefore unresponsive to IFN-{gamma}. To determine whether the regulation of IFN-{gamma}R2 expression, and therefore IFN-{gamma} responsiveness, is important for the differentiation of naive CD4+ T cells into Th1 cells or for Th1 effector function, we generated mice in which transgenic (TG) expression of IFN-{gamma}R2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-{gamma}R2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice also display several defects in Th1-dependent immunity in vivo, including attenuated delayed-type hypersensitivity responses and decreased antigen-specific IFN-{gamma} production. In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates. Together, these data suggest that the sustained expression of IFN-{gamma}R2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-{gamma}–unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.

Key Words: T helper type 1 cells, interferon type II, interferon receptors, hypersensitivity, delayed, cytokines


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