Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine
Jaeu Yi1,2, Jisun Jung1,2, Daehee Han1,2, Charles D. Surh1,2,3, You Jeong Lee1,2,*
1Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37673, Korea, 2Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Korea, 3Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, CA 92037, USA
*Correspondence: youjeong77@postech.ac.kr
Received November 11, 2018; Revised December 16, 2018; Accepted December 17, 2018.; Published online February 8, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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ABSTRACT
CD4 T cells differentiate into RORγt/IL-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from na?ve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that na?ve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.
Keywords: antigen-specific CD4 T cells, germ-free mice, segmented filamentous bacteria, single cell RT-PCR, small intestine


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