Suppression by T sub(FR) cells leads to durable and selective inhibition of B cell effector function

• Published in: Nature immunology Vol. 17; no. 12; pp. 1436 - 1446
• Main Authors: Sage, Peter T, Ron-Harel, Noga, Juneja, Vikram R, Sen, Debattama R, Maleri, Seth, Sungnak, Waradon, Kuchroo, Vijay K, Haining, W Nicholas, Chevrier, Nicolas, Haigis, Marcia, Sharpe, Arlene H
• Format: Journal Article
• Language: English
• Published: 01.12.2016
• ISSN: 1529-2908
• DOI: 10.1038/ni.3578

Follicular regulatory T cells (T sub(FR) cells) inhibit follicular helper T cell (T sub(FH) cell)-mediated antibody production. The mechanisms by which T sub(FR) cells exert their key immunoregulatory functions are largely unknown. Here we found that T sub(FR) cells induced a distinct suppressive state in T sub(FH) cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by T sub(FR) cells was durable and persisted even in the absence of T sub(FR) cells. This durable suppression was due in part to epigenetic changes. The cytokine IL-21 was able to overcome T sub(FR) cell-mediated suppression and inhibited T sub(FR) cells and stimulated B cells. By determining mechanisms of T sub(FR) cell-mediated suppression, we have identified methods for modulating the function of T sub(FR) cells and antibody production.