WSX-1 is required for the initiation of Th1 responses and resistance to L-major infection

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 wa s reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation i n vitro to induce Th1 differentiation but was normal in fully differentiate d and activated WSX-1(-/-) Th1 cells that had received secondary stimulatio n. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infectio n, showing impaired IFN-gamma production early in the infection. However, I FN-gamma production during the later phases of the infection was not impair ed in the knockout. WSX-1(-/-) mice also showed poorly differentiated granu lomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus,WSX-1 is essential for the initial mou nting of Th1 responses but dispensable for their maintenance.