TY - JOUR
T1 - Interferon γ signaling alters the function of T helper type 1 cells
AU - Tau, Gregory Z.
AU - Von Der Weid, Thierry
AU - Lu, Binfeng
AU - Cowan, Simone
AU - Kvatyuk, Marina
AU - Pernis, Alessandra
AU - Cattoretti, Giorgio
AU - Braunstein, Ned S.
AU - Coffman, Robert L.
AU - Rothman, Paul B.
PY - 2000/10/2
Y1 - 2000/10/2
N2 - 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 γ receptor (IFN-γR), whereas Th1 cells do not express the second chain of the IFN-γR (IFN-γR2) and are therefore unresponsive to IFN-γ. To determine whether the regulation of IFN-γR2 expression, and therefore IFN-γ 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-γR2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-γR2 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-γ 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-γR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-γ-unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.
AB - 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 γ receptor (IFN-γR), whereas Th1 cells do not express the second chain of the IFN-γR (IFN-γR2) and are therefore unresponsive to IFN-γ. To determine whether the regulation of IFN-γR2 expression, and therefore IFN-γ 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-γR2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-γR2 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-γ 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-γR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-γ-unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.
KW - Cytokines
KW - Hypersensitivity, delayed
KW - Interferon receptors
KW - Interferon type II
KW - T helper type 1 cells
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U2 - 10.1084/jem.192.7.977
DO - 10.1084/jem.192.7.977
M3 - Article
C2 - 11015439
AN - SCOPUS:0034596817
SN - 0022-1007
VL - 192
SP - 977
EP - 986
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -