T Cell Proliferation and Colitis Are Initiated by Defined Intestinal Microbes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Pailin ChiaranuntTimothy W Hand

Abstract

Inflammatory bowel disease has been associated with the dysregulation of T cells specific to Ags derived from the intestinal microbiota. How microbiota-specific T cells are regulated is not completely clear but is believed to be mediated by a combination of IgA, regulatory T cells, and type 3 innate lymphoid cells. To test the role of these regulatory components on microbiota-specific T cells, we bred CBir1 TCR transgenic (CBir1Tg) mice (specific to flagellin from common intestinal bacteria) onto a lymphopenic Rag1-/- background. Surprisingly, T cells from CBir1Tg mice bred onto a Rag1-/- background could not induce colitis and did not differentiate to become effectors under lymphopenic conditions, despite deficits in immunoregulatory factors, such as IgA, regulatory T cells, and type 3 innate lymphoid cells. In fact, upon transfer of conventional CBir1Tg T cells into lymphopenic mice, the vast majority of proliferating T cells responded to Ags other than CBir1 flagellin, including those found on other bacteria, such as Helicobacter spp. Thus, we discovered a caveat in the CBir1Tg model within our animal facility that illustrates the limitations of using TCR transgenics at mucosal surfaces, where multiple TCR specificities can ...Continue Reading

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Feb 2, 2020·Nature Reviews. Immunology·Roberta CarusoGabriel Núñez
Dec 14, 2018·Frontiers in Immunology·Chiara SoriniEduardo J Villablanca
Nov 29, 2020·Scandinavian Journal of Immunology·Gabriela Fonseca-CamarilloJesús K Yamamoto-Furusho

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