CD161⁺ Tconv and CD161⁺ treg share a transcriptional and functional phenotype despite limited overlap in TCRβ repertoire

Abstract

© 2017 Duurland, Brown, O'Shaughnessy and Wedderburn. Human regulatory T cells (Treg) are important in immune regulation, but can also show plasticity in specific settings. CD161 is a lectin-like receptor and its expression identifies an effector-like Treg population. Here, we determined how CD161 + Treg relate to CD161 + conventional T cells (Tconv). Transcriptional profiling identified a shared transcriptional signature between CD161 + Tconv and CD161 + Treg, which is associated with T helper (Th)1 and Th17 cells, and tissue homing, including high expression of gut-homing receptors. Upon retinoic acid (RA) exposure, CD161 + T cells were more enriched for CCR9 + and integrin α4 + β7 + cells than CD161 - T cells. In addition, CD161 + Tconv and CD161 + Treg were enriched at the inflamed site in autoimmune arthritis, and both CD161 + and CD161 - Treg from the inflamed site were suppressive in vitro. CD161 + T cells from the site of autoimmune arthritis showed a diminished gut-homing phenotype and blunted response to RA suggesting prior imprinting by RA in the gut or at peripheral sites rather than during synovial inflammation. TCRβ repertoires of CD161 + and CD161 - Tconv and Treg from blood showed limited overlap whereas there was clear overlap between CD161 + and CD161 - Tconv, and CD161 + and CD161 - Treg from the inflamed site suggesting that the inflamed environment may alter CD161 levels, potentially contributing to disease pathogenesis.