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JCI Insight. 2019 Oct 17;4(20). pii: 130062. doi: 10.1172/jci.insight.130062.

PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21.

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Division of Rheumatology, Immunology, and Allergy.
Department of Surgery.
Center for Data Sciences, and.
Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, Massachusetts, USA.
Oncology & Immunology Discovery, and.
Genetics and Pharmacogenomics, Merck & Co. Inc., Boston, Massachusetts, USA.
Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA.
Division of Rheumatology, New York University School of Medicine, New York, New York, USA.
Department of Microbiology & Immunology and Division of Rheumatology, Albert Einstein College of Medicine, Bronx, New York, USA.
Rheumatology Division and Russell/Engleman Research Center, UCSF, San Francisco, California, USA.
Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA.
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA.
Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.


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 disease activity and the frequency of CD11c+ B cells in SLE patients. PD-1hiCD4+ T cells were found within lupus nephritis kidneys and correlated with B cell numbers in the kidney. Both IL-21 neutralization and CRISPR-mediated deletion of MAF abrogated the ability of Tph cells to induce memory B cell differentiation into plasmablasts in vitro. These findings identify Tph cells as a highly expanded T cell population in SLE and suggest a key role for Tph cells in stimulating pathologic B cell responses.


Adaptive immunity; Autoimmunity; Immunology; Lupus; T cells

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