Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis

Journal article

CD4+ T cells are central mediators of autoimmune pathology; however, the definition of their key effector functions in specific autoimmune diseases remains limited. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation1. We applied this approach to joint tissue in rheumatoid arthritis (RA), a chronic immune7ediated arthritis that affects up to 1% of the population2. Utilizing mass cytometry to detect activated T cells in RA synovial tissue revealed a strikingly expanded population of PD-1hi CXCR5- CD4+ T cells. These cells are not exhausted, Rather, multidimensional cytometry, transcriptomics, and functional assays define a population of PD-1hi CXCR5- ‘peripheral helper’ T (Tph) cells that express factors enabling B cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hi CXCR5+ T ‘follicular helper’ (Tfh) cells, Tph cells induce plasma cell differentiation in vitro via IL-21 and SLAMF5-interactions3,4. However, global transcriptomics robustly separate Tph cells from Tfh cells, with altered expression of Bcl6 and Blimp-1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in Tph cells. Tph cells appear uniquely poised to promote B cell responses and antibody production within pathologically inflamed non-lymphoid tissues.

Authors: Rao, DA; Gurish, MF; Marshall, JL; Slowikowski, K; Fonseka, CY

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Publishing Group
• Journal: Nature
• Volume: 542
• Issue: 7639
• Pages: 110-114
• Publication date: 2017-02-01
• Acceptance date: 2016-11-18
• DOI: 10.1038/nature20810
• ISSN: 0028-0836, 1476-4687
• Keywords: mass cytometry; CCR2; plasma cells; PD-1; follicular helper T cells; rheumatoid arthritis