Abstract
Peripheral helper T (TPH) cells are a recently identified Th cell subset that promotes B cell differentiation and antibody production in inflamed tissues. This study investigated circulating TPH cells to determine their involvement in systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells collected from SLE patients and healthy individuals were analysed. TPH cells were identified as CD3+CD4+CD45RA-CXCR5- cells with a high expression of PD-1. The frequency, activation status and subsets of TPH cells were evaluated by flow cytometry. The production of IL-21 was assessed by intracellular staining and the association of TPH cells with disease activity and B cell populations was determined. Circulating TPH cells, identified as CD3+CD4+CD45RA-PD-1highCXCR5- cells were increased in the peripheral blood of SLE patients compared with controls. Circulating TPH cells produced similar amounts of IL-21 compared with follicular Th cells. The expansion and activation of TPH cells were correlated with SLE disease activity. Activated TPH cells, particularly Th1-type TPH cells, were associated with the promotion of B cell differentiation in SLE patients. The association of TPH cells with disease activity suggests the involvement of extrafollicular T-B cell interactions in the pathogenesis of SLE. TPH cells promote autoantibody production in aberrant lymphoid organs and therefore might be a novel therapeutic target in autoantibody-producing disorders.
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