Help not wanted in the joint

See allHide authors and affiliations

Science Immunology  03 Mar 2017:
Vol. 2, Issue 9, eaan0289
DOI: 10.1126/sciimmunol.aan0289


A newly discovered T cell subset that helps B cells is expanded in joints of rheumatoid arthritis patients.

CD4+ T cells and B cells contribute to inflammation in the joints of rheumatoid arthritis (RA) patients, but the precise roles of these lymphocytes in disease pathogenesis are not known. A recent report by Rao et al. characterizes a newly defined subset of CD4+ T cells that are expanded in RA joints and are likely peripheral helpers of autoreactive B cells.

Synovial tissues and fluid sampled from seropositive RA patients (i.e., with anti-Ig Fc or anti–citrullinated peptide autoantibodies) and from seronegative patients were analyzed by mass cytometry, fluorescence flow cytometry, reverse transcription polymerase chain reaction, and unbiased RNA sequencing. About 25 to 30% of the CD4+ T cells from seropositive patient samples expressed high levels of programmed cell death protein-1 (PD-1), five times the number in seronegative patient samples. Unlike T follicular helper (TFH) cells, which express PD-1 and CXCR5, the expanded PD-1hi T cells were CXCR5 negative. PD-1hiCXCR5 CD4+ T cells were also detected in the blood of seropositive patients, and their numbers correlated with disease activity.

The PD-1hiCXCR5 T cells from the RA patients expressed much more IL-21 and CXCL13 than PD-1 cells, as well as many of the genes important in T-B collaboration that TFH cell express. Unlike TFH cells, PD-1hiCXCR5 T cells had high BLIMP1and low BCL6 expression and also expressed the inflammatory chemokine receptors CCR2, CX3CR1, and CCR5. Coculture experiments demonstrated that the PD-1hiCXCR5 T cells supported B cell differentiation into plasma cells and IgG secretion. Immunofluorescence studies of synovial tissues showed that many of these PD-1hiCXCR5 T cells were adjacent to B cells, inside and outside lymphoid aggregates.

The T cells in the joints RA patients described in this study, which the authors call T peripheral helper (TPH) cells, have the functional properties of TFH cells found in secondary lymphoid organs, and the migratory phenotype of effector T cells found in inflamed tissues. Thus, it appears they are highly qualified to provide T cell help for local autoantibody production in the rheumatic joint. TPH cells may be important to the development of germinal centers in tertiary lymphoid organs, a characteristic feature of the synovium in RA. The presence of TPH cells in other chronic autoimmune diseases and the role of these cells in disease pathogenesis remain to be determined.

Highlighted Article

Stay Connected to Science Immunology

Navigate This Article