Lymphedema pathogenesis involves antigen-driven expansion of CD4(+) T cells in skin Journal Article
| Authors: | Campbell, A. C.; Stull-Lane, A. R.; Baik, J. E.; Sarker, A.; Shin, J.; Ashokan, G.; Park, H. J.; Pollack, B. L.; Pakkerakari, P.; Parisotto, Y. F.; Roberts, A.; Brown, C. C.; Mehrara, B. J.; Kataru, R. P. |
| Article Title: | Lymphedema pathogenesis involves antigen-driven expansion of CD4(+) T cells in skin |
| Abstract: | Introduction: Lymphedema, a progressive condition involving unresolved swelling and inflammation, affects as many as 1 in 1000 Americans. Although CD4+ T cells are implicated in the chronic inflammatory process, antigen-specific responses are understudied. Methods: Using high-throughput sequencing, we studied the T cell receptors (TCRs) of CD4+ T cells in paired normal and lymphedema skin biopsies of 11 patients. We also employed in vitro studies using human samples and cells from a lymphedema mouse model. Results: Target epitopes of the TCRs, including the antigen insulin, were identified. Clonality was significantly higher in lymphedema samples than in controls, both in human samples and a mouse model of the disease. In vitro studies using human samples and a lymphedema mouse model demonstrated increased activated memory T cell responses specific to the antigen insulin compared with the control. Discussion: Our study highlights an oligoclonal expansion of CD4+ T cells in lymphedema and supports insulin as a probable antigen driving T cell responses. These findings can help inform more precise therapeutic targets for the development of better therapies and preventative tools to combat lymphedema progression. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adult; clinical article; controlled study; human tissue; protein expression; middle aged; human cell; histopathology; pathogenesis; nonhuman; t cells; t lymphocyte; mouse; breast cancer; gene expression; skin biopsy; animal experiment; animal model; inflammation; obesity; in vitro study; histology; lymphedema; skin; t lymphocyte receptor; body mass; clonal variation; cd4+ t lymphocyte; epitope; insulin; disease duration; cell expansion; peripheral blood mononuclear cell; skin cell; memory t lymphocyte; etiology; high throughput sequencing; human; female; article; oligoclonality; breast cancer-related lymphedema; antigen-specific responses; cd4+ t cell negative isolation kit; graphpad prism v8; imagej software; immunoseq analyzer; immunoseq analyzer 3.0 software; qiaamp dna ffpe tissue kit |
| Journal Title: | Frontiers in Immunology |
| Volume: | 16 |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2025-07-31 |
| Start Page: | 1620571 |
| Language: | English |
| DOI: | 10.3389/fimmu.2025.1620571 |
| PUBMED: | 40821816 |
| PROVIDER: | scopus |
| PMCID: | PMC12354532 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Raghu P. Kataru -- Source: Scopus |
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