Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen

TY - JOUR

T1 - Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen

AU - Ariotti, S.

AU - Beltman, J.B.

AU - Chodaczek, G.

AU - Hoekstra, M.E.

AU - van Beek, A.E.

AU - Gomez-Eerland, R.

AU - Ritsma, L.

AU - van Rheenen, J.

AU - Maree, A.F.

AU - Zal, T.

AU - de Boer, R.J.

AU - Haanen, J.B.

AU - Schumacher, T.N.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8(+) T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site.

AB - Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8(+) T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site.

U2 - 10.1073/pnas.1208927109

DO - 10.1073/pnas.1208927109

M3 - Article

SN - 0027-8424

VL - 109

SP - 19739

EP - 19744

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 48

ER -