An alternate pathway for type 1 T cell differentiation

C Feng1, S Watanabe, S Maruyama

  • 1Department of Microbiology and Immunology, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan.

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.

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