Abnormal expansion of peripheral helper T cells in primary immune thrombocytopenia

Peripheral helper T (Tph) cells, a distinct T-cell subset defined as CD4⁺PD-1^hiCXCR5^- phenotypically, are increasingly recognized as key drivers of antibody-mediated autoimmunity; however, their role in primary immune thrombocytopenia (ITP) remains poorly defined. In this study, we evaluated circulating Tph cells in newly diagnosed ITP and characterized their dynamic changes following dexamethasone therapy. Circulating Tph cells were significantly expanded in patients with ITP and were positively correlated with bleeding severity, suggesting involvement of Tph cells in ITP pathophysiology. High-dose dexamethasone markedly reduced circulating Tph frequencies both <i>in vitro</i> and <i>in vivo</i>. Notably, persistently elevated Tph levels were observed in patients who were non-responsive to dexamethasone. Furthermore, plasma interleukin-21 levels declined in parallel with Tph reduction following dexamethasone treatment, and were positively correlated with Tph frequencies in untreated, newly diagnosed ITP patients, consistent with Tph-associated B-cell helper activity. Collectively, these findings identify Tph cells as a potential indicator of extrafollicular B-cell activation in ITP and highlight their relevance to dexamethasone therapeutic responsiveness.