Rao, DeepakGurish, Michael F.Marshall, Jennifer L.Slowikowski, KamilFonseka, Chamith Y.Liu, YanyanDonlin, Laura T.Henderson, LaurenWei, KevinMizoguchi, FumitakaTeslovich, NikolaWeinblatt, MichaelMassarotti, ElenaCoblyn, JonathanHelfgott, SimonLee, Yvonne C.Todd, DerrickBykerk, Vivian P.Goodman, Susan M.Pernis, Alessandra B.Ivashkiv, Lionel B.Karlson, ElizabethNigrovic, PeterFiler, AndrewBuckley, Christopher D.Lederer, JamesRaychaudhuri, SoumyaBrenner, Michael2022-07-222017-02-02Rao, Deepak, Michael F. Gurish, Jennifer L. Marshall, Kamil Slowikowski, Chamith Y. Fonseka, Yanyan Liu, Laura T. Donlin et al. "Pathologically Expanded Peripheral T Helper Cell Subset Drives B Cells in Rheumatoid Arthritis." Nature 542, no. 7639 (2017): 110-114. DOI: 10.1038/nature208100028-08361476-4687https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372829CD4+ T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation1. Here, we used mass cytometry to evaluate activated T cells in joint tissue from patients with rheumatoid arthritis (RA), a chronic immune-mediated arthritis that affects up to 1% of the population2. This approach revealed a strikingly expanded population of PD-1hi CXCR5- CD4+ T cells in RA synovium. 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.en-USMultidisciplinaryJournal Article2016-11-1020162022-07-2210.1038/nature20810