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 CD103—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.