Data from: Lymph node transplantation decreases swelling and restores immune responses in a transgenic model of lymphedema

Introduction: Secondary lymphedema is a common complication of cancer
treatment and recent studies have demonstrated that lymph node
transplantation (LNT) can decrease swelling, as well as the incidence of
infections. However, although these results are exciting, the mechanisms
by which LNT improves these pathologic findings of lymphedema remain
unknown. Using a transgenic mouse model of lymphedema, this study sought
to analyze the effect of LNT on lymphatic regeneration and T cell-mediated
immune responses. Methods: We used a mouse model in which the expression
of the human diphtheria toxin receptor is driven by the FLT4 promoter to
enable the local ablation of the lymphatic system through subdermal
hindlimb diphtheria toxin injections. Popliteal lymph node dissection was
subsequently performed after a two-week recovery period, followed by
either orthotopic LNT or sham surgery after an additional two weeks.
Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking,
and T cell-mediated immune responses were analyzed 10 weeks later.
Results: LNT resulted in a marked decrease in hindlimb swelling,
fibroadipose tissue deposition, and decreased accumulation of
perilymphatic inflammatory cells, as compared to controls. In addition,
LNT induced a marked lymphangiogenic response in both capillary and
collecting lymphatic vessels. Interestingly, the resultant regenerated
lymphatics were abnormal in appearance on lymphangiography, but LNT also
led to a notable increase in dendritic cell trafficking from the periphery
to the inguinal lymph nodes and improved adaptive immune responses.
Conclusions: LNT decreases pathological changes of lymphedema and was
shown to potently induce lymphangiogenesis. Lymphatic vessels induced by
LNT were abnormal in appearance, but were functional and able to transport
antigen-presenting cells. Animals treated with LNT have an increased
ability to mount T cell-mediated immune responses when sensitized to
antigens in the affected hindlimb.