Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo.
The transcription factor interferon regulatory factor-1 (IRF-1) mediates the effects of IFN. No information exists on its role in lymphokine production. Protection against the intracellular pathogen Leishmania major depends on a Th1 response. Here, we show that CD4+ T cells from Leishmania-infected mice lacking one (+/-) or both (-/-) alleles of the IRF-1 gene developed a profound, gene dose-dependent decrease in IFNgamma production. IRF-1(-/-) mice showed dramatically exacerbated Leishmaniasis. They produced increased Leishmania-specific IgG1 and IgE, and their CD4+ T cells produced increased IL-4, characteristics of the non-protective Th2 response. In cell transfer experiments, IRF-1(-/-) CD4+ T cells mounted normal Th1 responses. However, the ability of IRF-1(-/-) mice to produce IL-12 was severely compromised. Thus, IRF-1 is a determining factor for Th1 responses.
Lohoff
M
M
Ontario Cancer Institute, and the Department of Immunology, University of Toronto, Canada.
Ferrick
D
D
Mittrucker
H W
HW
Duncan
G S
GS
Bischof
S
S
Rollinghoff
M
M
Mak
T W
TW
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D018664:Interleukin-12 / Q000096:biosynthesis; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000502:physiology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D018664:Interleukin-12