Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen

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Science Immunology  08 Feb 2019:
Vol. 4, Issue 32, eaau9079
DOI: 10.1126/sciimmunol.aau9079

Dietary modulation of T cell immunity

Commensal intestinal bacteria respond to dietary changes by modifying gene expression, leading to shifts in the levels of bacterial antigens encountered by the intestinal immune system. Wegorzewska et al. developed a mouse model system to investigate whether CD4+ T cell recognition of protein antigens of the gut symbiont Bacteroides thetaiotaomicron is subject to dietary modulation. TCR transgenic T cells for an outer membrane vesicle protein differentiated into both regulatory and effector T cells, with colitis emerging after selective regulatory T cell depletion. Dietary glucose was observed to strongly repress the T cell–detected antigen. These findings suggest that dietary modifications that reduce expression of immunodominant antigens targeted by T cells could help ameliorate some forms of human inflammatory bowel disease.


T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B. theta–colonized healthy mice and differentiated into regulatory T cells (Tregs) and effector T cells (Teffs). Depletion of B. theta–specific Tregs resulted in colitis, showing that a single protein expressed by B. theta can drive differentiation of Tregs that self-regulate Teffs to prevent disease. We found that BθOM T cells recognized a peptide derived from a single B. theta protein, BT4295, whose expression is regulated by nutrients, with glucose being a strong catabolite repressor. Mice fed a high-glucose diet had a greatly reduced activation of BθOM T cells in the colon. These studies establish that the immune response to specific bacterial antigens can be modified by changes in the diet by altering antigen expression in the microbe.

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