Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis

Lymphedema is a progressive condition accompanying cellulitis and angiosarcoma, suggesting its association with immune dysfunction. Lymphatic venous anastomosis (LVA) can provide relief from cellulitis and angiosarcoma. However, the immune status of peripheral T cells during lymphedema and post-LVA remains poorly understood. Using peripheral blood T cells from lymphedema, post-LVA, and healthy controls (HCs), we compared the profile of T cell subsets and T cell receptor (TCR) diversity. PD-1⁺ Tim-3 ⁺ expression was downregulated in post-LVA compared with lymphedema. IFN-γ levels in CD4⁺PD-1⁺ T cells and IL-17A levels in CD4⁺ T cells were downregulated in post-LVA compared with lymphedema. TCR diversity was decreased in lymphedema compared with HCs; such TCR skewing was drastically improved in post-LVA. T cells in lymphedema were associated with exhaustion, inflammation, and diminished diversity, which were relieved post-LVA. The results provide insights into the peripheral T cell population in lymphedema and highlight the immune modulatory importance of LVA.