Potent intestinal Th17 priming through peripheral lipopolysaccharide-based immunization

Journal of Leukocyte Biology

Martin Oft²  Anthony T. Vella¹  Bei Liu¹  Soo-Mun Ngoi¹  Jie Dai²  Jeremy P. McAleer¹  Zihai Li¹ 

[1] Department of Immunology, The University of Connecticut Health Center, Farmington, Connecticut, USA; and Department of Immunology, The University of Connecticut Health Center, Farmington, Connecticut, USA; and Department of Immunology, The University of Connecticut Health Center, Farmington, Connecticut, USA; and;Schering-Plough Biopharma, Palo Alto, California, USA Schering-Plough Biopharma, Palo Alto, California, USA Schering-Plough Biopharma, Palo Alto, California, USA

关键词: T Cells;    vaccination;    superantigens;    cell differentiation;   

DOI  :  10.1189/jlb.0909631

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Lipopolysaccharide (LPS) is a potent natural adjuvant, commonly used to amplify Th1 responses. Here, we report that systemic immunization using LPS generates large numbers of specific Th17 cells in murine small intestinal lamina propria. The priming of these Th17 cells required IL-23p19 production by bone marrow-derived cells. In contrast, IL-23 had no impact on Th1 differentiation or overall numbers of Ag-specific regulatory T cells. Experiments using T-cell adoptive transfers revealed a previously unappreciated mechanism for how Th17 responses are amplified in vivo: stimulation through LPS expanded precommitted Th17 cells rather than causing Th17 differentiation. Second, LPS drove Th17 cell expansion independently of IL-23, demonstrating that this cytokine is not necessary for expansion and possibly functions at an earlier stage in Th17 priming. Our data provide an impetus for using LPS-based peripheral vaccination to augment specific T-cell-mediated immunity in the gut mucosa.

【 授权许可】

Unknown