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

doi:10.1016/j.isci.2023.106822

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

iScience. 2023 May 6;26(6):106822. doi: 10.1016/j.isci.2023.106822. eCollection 2023 Jun 16.

Authors

Hirofumi Imai¹, Takakazu Kawase^{2

3}, Shuhei Yoshida¹, Toshiro Mese¹, Solji Roh¹, Asuka Fujita⁴, Toshio Uchiki⁴, Ayano Sasaki⁴, Shogo Nagamatsu⁴, Atsushi Takazawa⁵, Tatsuo Ichinohe², Isao Koshima^{1

4}

Affiliations

¹ International Center for Lymphedema, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
² Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
³ International Center for Cell and Gene Therapy, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
⁴ Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
⁵ Department of Orthopaedic Surgery, Hiroshima Hiramatsu Hospital, Hiroshima 732-0816, Japan.

Abstract

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.

Keywords: Components of the immune system; Health sciences; Immunology.