期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 7, 页码 977-986出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.7.977
关键词
T helper type 1 cells; interferon type II; interferon receptors; hypersensitivity, delayed; cytokines
资金
- NIAID NIH HHS [P01AI39675] Funding Source: Medline
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 Thl 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.
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