Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis
Hirofumi Imai,
Takakazu Kawase,
Shuhei Yoshida,
Toshiro Mese,
Solji Roh,
Asuka Fujita,
Toshio Uchiki,
Ayano Sasaki,
Shogo Nagamatsu,
Atsushi Takazawa,
Tatsuo Ichinohe,
Isao Koshima
Affiliations
Hirofumi Imai
International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan; Corresponding author
Takakazu Kawase
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan; International Center for Cell and Gene Therapy, Fujita Health University, Toyoake, Aichi 470-1192, Japan
Shuhei Yoshida
International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Toshiro Mese
International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Solji Roh
International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Asuka Fujita
Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Toshio Uchiki
Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Ayano Sasaki
Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Shogo Nagamatsu
Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Atsushi Takazawa
Department of Orthopaedic Surgery, Hiroshima Hiramatsu Hospital, Hiroshima 732-0816, Japan
Tatsuo Ichinohe
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan
Isao Koshima
International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan; Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Summary: 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.