Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4+ T Cell Engulfment Process

CD4(+) T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4(+) lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4(+) T cells in hepatocytes. Enclysis is selective for CD4(+) but not CD8(+) cells, independent of antigen-specific activation, and occurs in human hepatocytes in vitro, ex vivo, and in vivo. Intercellular adhesion molecule 1 (ICAM-1) facilitates T cell early adhesion and internalization, whereas hepatocytes form membrane lamellipodia or blebs to mediate engulfment. T cell internalization is unaffected by wortmannin and Rho kinase inhibition. Hepatocytes engulf Treg cells more efficiently than non-Treg cells, but Treg cell-containing vesicles preferentially acidify overnight. Thus, enclysis is a biological process with potential effects on immunomodulation and opens a new field for research to fully understand CD4(+) T cell dynamics in liver inflammation.