WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. |
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Authors: | H Yoshida S Hamano G Senaldi T Covey R Faggioni S Mu M Xia A C Wakeham H Nishina J Potter C J Saris T W Mak |
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Affiliation: | The Amgen Institute, Toronto, Ontario M5G 2C1, Canada |
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Abstract: | WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors. The physiological role of WSX-1, which is expressed mainly in T cells, was investigated in gene-targeted WSX-1-deficient mice. IFN-gamma production was reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation in vitro to induce Th1 differentiation but was normal in fully differentiated and activated WSX-1(-/-) Th1 cells that had received secondary stimulation. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infection, showing impaired IFN-gamma production early in the infection. However, IFN-gamma production during the later phases of the infection was not impaired in the knockout. WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus, WSX-1 is essential for the initial mounting of Th1 responses but dispensable for their maintenance. |
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