Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine

• Published in: Molecules and cells Vol. 42; no. 3; pp. 228 - 236
• Main Authors: Yi, Jaeu, Jung, Jisun, Han, Daehee, Surh, Charles D, Lee, You Jeong
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 31.03.2019; 한국분자세포생물학회
• Subjects: Animals; Antigens - metabolism; Bacteria - growth & development; Bacteria - metabolism; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Colony Count, Microbial; Feces - microbiology; Intestine, Small - immunology; Intestine, Small - microbiology; Intestine, Small - ultrastructure; Mice, Inbred C57BL; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stochastic Processes; Transcription, Genetic; 생물학; segmented filamentous bacteria; single cell RT-PCR; small intestine; antigen-specific CD4 T cells; germ-free mice
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2018.0424

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 naïve 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 naïve 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 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.