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CD4+ T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema.

Gabriela D García Nores | Catherine L Ly | Daniel A Cuzzone | Raghu P Kataru | Geoffrey E Hespe | Jeremy S Torrisi | Jung Ju Huang | Jason C Gardenier | Ira L Savetsky | Matthew D Nitti | Jessie Z Yu | Sonia Rehal | Babak J Mehrara
Nature communications | 2018

T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells. CD4+ T cell activation is associated with differentiation into a mixed T helper type 1 and 2 phenotype, as well as upregulation of adhesion molecules and chemokines that promote migration to the skin. Most importantly, we find that blocking T cell release from lymph nodes using a sphingosine-1-phosphate receptor modulator prevents lymphedema, suggesting that this approach may have clinical utility.

Pubmed ID: 29773802

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R21 CA194882
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009501
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009685
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL111130

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