Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids.

Liver-resident CD8(+) T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: How can these liver CD8(+) T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD 103-a key integrin for T cell residence in epithelial tissues-we investigated other candidate adhesion molecules. Using intravital imaging, we found that CD8(+) T cell patrolling in the hepatic sinusoids is dependent on LFA-1-ICAM-1 (intercellular adhesion molecule-1) interactions. Liver-resident CD8(+) T cells up-regulate LFA-1 compared with effector memory cells, presumably to facilitate this behavior. Last, we found that LFA-1-deficient CD8(+) T cells failed to form substantial liver-resident memory populations after Plasmodium immunization or lymphocytic choriomeningitis virus infection. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8(+) T cells to patrol and remain in the hepatic sinusoids.