biostudies-literatureBocharnikov AVNIAMSRheumatology Research FoundationBurroughs Wellcome FundLupus Research AllianceNIAMS NIH HHS130062https://www.ebi.ac.uk/biostudies/studies/S-EPMC6824311biostudies-literatureUnknown4(20)Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell-B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1hiCXCR5-CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1hiCXCR5-CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5- T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical diseaJCI insightPD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21.PMC6824311Career Award in Medical SciencesR01 AR065538Scientist Development AwardUH2 AR067679AR072791AR065538AR070253P30 AR070253K08 AR072791Target Identification in LupusWacleche VSWofsy DDiamond BGurish MFPetri MWang GGuthridge JMLi ZJArazi ABuyon JPKeras GLederer JAMuise ESQu YAccelerating Medicines Partnership (AMP) RA/SLE NetworkCostenbader KHJames JAMackey MFRao DAAnolik JHNigrovic PAFonseka CYKeegan JZhang KXAlves SEPutterman CBrenner MBCao YBocharnikov AVfalsePD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell-B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1hiCXCR5-CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1hiCXCR5-CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5- T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical disea2019-01-01T00:00:00Z2019 Oct2025-04-05T13:31:09.299Z2019-11-15T08:04:51ZS-EPMC68243113153648010.1172/jci.insight.130062