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An alternate pathway for type 1 T cell differentiation.


Int Immunol. 1999 Aug;11(8):1185-94. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Animal Cell Differentiation DNA-Binding Proteins/GENETICS/*METABOLISM Enzyme-Linked Immunosorbent Assay Gene Expression Regulation Interferon Type II/*BIOSYNTHESIS Interleukin-12/GENETICS/*METABOLISM Interleukin-18/GENETICS/METABOLISM Leishmania major/IMMUNOLOGY Leishmaniasis, Cutaneous/IMMUNOLOGY Listeria Infections/IMMUNOLOGY Macrophages, Peritoneal/*IMMUNOLOGY Malaria/IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Inbred C57BL Phosphoproteins/GENETICS/*METABOLISM Plasmodium berghei Reverse Transcriptase Polymerase Chain Reaction Spleen/CYTOLOGY/IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/*CYTOLOGY/*IMMUNOLOGY Transcription, Genetic


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