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 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.
Yoshida
H
H
The Amgen Institute, Toronto, Ontario M5G 2C1, Canada
Hamano
S
S
Senaldi
G
G
Covey
T
T
Faggioni
R
R
Mu
S
S
Xia
M
M
Wakeham
A C
AC
Nishina
H
H
Potter
J
J
Saris
C J
CJ
Mak
T W
TW
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D006099:Granuloma / Q000473:pathology; D006413:Hematopoietic System / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008208:Lymphatic System / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000473:pathology
C484747:Il27ra protein, mouse; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D015847:Interleukin-4; D007371:Interferon-gamma