Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses.

J Exp Med. 2000 May 1;191(9):1605-10. Unique Identifier : AIDSLINE MED/20253246
He J; Gurunathan S; Iwasaki A; Ash-Shaheed B; Kelsall BL; Immune Cell Interaction Unit, Mucosal Immunity Section,; Laboratory of Clinical Investigation, National Institute of; Allergy and Infectious Diseases, National Institutes of Health,; Bethesda, MD 20892, USA.

Abstract: We explored the role of Gi protein signaling in the regulation of interleukin (IL)-12 production and T helper cell type 1 (Th1) T cell differentiation. In initial studies, we showed that treatment of normal mice with pertussis toxin (PT), which inhibits Gi protein signaling, enhanced the capacity of splenocytes to produce IL-12 in response to both microbial and nonmicrobial stimuli. In addition, PT treatment increased the production of tumor necrosis factor (TNF)-alpha and IL-10 by stimulated cells. These findings were corroborated by the fact that untreated Gi2alpha(2/-) mice exhibited enhanced production of IL-12 and TNF-alpha by splenocytes, and of IL-12 p40 by purified spleen CD8alpha(+) lymphoid dendritic cells. Finally, we showed that while normal BALB/c mice infected with Leishmania major exhibited a nonhealing phenotype, those treated with PT when infection was initiated exhibited a healing phenotype along with an enhancement of leishmania-specific Th1 responses in draining lymph nodes. Further, healing was prevented by coadministration of anti-IL-12 and PT. These data demonstrate that endogenous Gi protein signaling has a primary role in the regulation of IL-12 production and the induction of Th1 responses in vivo.

Keywords: JOURNAL ARTICLE Adenosine Diphosphate Ribose/METABOLISM Animal Antigens, CD8 Cell Differentiation Dendritic Cells/IMMUNOLOGY G-Protein, Inhibitory Gi/GENETICS/*METABOLISM Interferon Type II/BIOSYNTHESIS Interleukin-10/BIOSYNTHESIS Interleukin-12/*BIOSYNTHESIS Interleukin-4/BIOSYNTHESIS Leishmaniasis, Cutaneous/IMMUNOLOGY Lymph Nodes/IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Mutant Strains Pertussis Toxins/PHARMACOLOGY Protein Processing, Post-Translational Signal Transduction Spleen/CYTOLOGY/DRUG EFFECTS Th1 Cells/*IMMUNOLOGY Tumor Necrosis Factor/BIOSYNTHESIS

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