An alternate pathway for type 1 T cell differentiation.
IFN-regulatory factor-1 (IRF-1) gene-disrupted mice are defective in IL-12 and IL-18 gene expression at the transcriptional and post-translational level respectively. The mutant mouse mounts a type 2 T cell response upon bacterial infection because of the impaired induction of the IL-12 p40 gene and IFN-gamma-producing type 1 T cells are not induced. We showed here, however, that different pathogens activate a novel pathway for inducing IFN-gamma-producing type 1 T cells even in an IRF-1-deficient mouse. This pathway is independent of IL-12 and IL-18, and is mediated by a distinct function of macrophage lineage cells. Macrophages of the mutant mice fail to activate the IL-12-dependent pathway, but they function in the IL-12-independent pathway in Plasmodium-infected mice. This leads to the hypothesis that the IL-12-independent novel pathway for inducing IFN-gamma-producing T cells is distinct from the classical type 1/type 2 T cell subset differentiation pathway.
Feng
C
C
Department of Microbiology and Immunology, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan.
Watanabe
S
S
Maruyama
S
S
Suzuki
G
G
Sato
M
M
Furuta
T
T
Kojima
S
S
Taki
S
S
Asano
Y
Y
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008288:Malaria / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010962:Plasmodium berghei; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D018664:Interleukin-12; D007371:Interferon-gamma