Figure 2.

Pathophysiologic sequence following CD4⁺ cell inflammation in lymphedema. A compromised lymphatic system leads to lymphatic fluid stasis, which subsequently contributes to the accumulation of a distinct CD4⁺ inflammatory infiltrate. Although there is a mixed Th1 and Th2 response, Th2 cells in particular have been found to be critical in the development of the pathologic findings of lymphedema. Th2 cytokines IL-4 and IL-13 contribute to lymphedema through the impairment of lymphangiogenesis and upregulation of TGF-β1, which promotes fibrosis. The accumulation of fibrotic components over time ultimately leads to lymphatic dysfunction.