Research ArticleIMMUNOLOGICAL MEMORY

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

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Science Immunology  17 Mar 2017:
Vol. 2, Issue 9, eaaj1996
DOI: 10.1126/sciimmunol.aaj1996

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LFA-1 helps T cells feel at home in the liver

Liver-resident T cells are critical to defense against infections such as malaria and hepatitis B virus. To protect the hepatic sinusoids, these cells must enter circulation yet still remain in the liver. McNamara et al. now report that liver-resident CD8+ T cells up-regulate LFA-1 and that LFA-1–ICAM-1 (intercellular adhesion molecule–1) interactions are critical for T cell patrolling of the hepatic sinusoids. Moreover, in the absence of LFA-1, CD8 T cells do not form liver-resident memory populations, even after infection with either Plasmodium or lymphocytic choriomeningitis virus. Thus, LFA-1 expression acts as a sort of invisible fence, allowing the liver-resident memory T cells free reign within the boundaries of the liver.

Abstract

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.

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