Different patterns of peripheral migration by memory CD4+ and CD8+ T cells

• Published in: Nature (London) Vol. 477; no. 7363; pp. 216 - 219
• Main Authors: Gebhardt, Thomas, Whitney, Paul G., Zaid, Ali, Mackay, Laura K., Brooks, Andrew G., Heath, William R., Carbone, Francis R., Mueller, Scott N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.09.2011; Nature Publishing Group
• Subjects: 631/250/1619/554; 631/250/2152/1566/1571; 631/80/84; 692/699/255/2514; Adoptive Transfer; Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Movement; E-Selectin - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genomic Imprinting; Herpes Simplex - immunology; Herpes Simplex - virology; Humanities and Social Sciences; Immunobiology; Immunologic Memory; Immunologic Surveillance - immunology; letter; Ligands; Mice; multidisciplinary; Organs and cells involved in the immune response; P-Selectin - metabolism; Science; Science (multidisciplinary); Simplexvirus - immunology; Skin - cytology; Skin - immunology; Skin - virology; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; Vertebrata; Mammalia; CD4 T lymphocyte; Immune response; Mouse; Cellular migration; Rodentia; Memory t cell; Cellular immunity; Immunity; CD8 T lymphocyte
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10339

T-cell migration is subset-specific T cells are crucial to immunity at surface tissues such as skin, which represent entry points for many infectious agents. Migration and targeting to these specific regions is thought to be a key to efficient immune protection. Gebhardt et al . provide evidence for differential migration of helper and killer T-cell subsets after local skin infection with herpes simplex virus, with helper and killer memory T cells segregating to dermis and epidermis respectively. CD4 + T cells, through their ability to access the circulation, are thought to be responsible for providing protection distal to the primary site of infection. Infections localized to peripheral tissues such as the skin result in the priming of T-cell responses that act to control pathogens. Activated T cells undergo migrational imprinting within the draining lymph nodes 1 , resulting in memory T cells that provide local and systemic protection 2 . Combinations of migrating and resident memory T cells have been implicated in long-term peripheral immunity, especially at the surfaces that form pathogen entry points into the body 3 . However, T-cell immunity consists of separate CD4 + helper T cells and CD8 + killer T cells, with distinct effector and memory programming requirements 4 . Whether these subsets also differ in their ability to form a migrating pool involved in peripheral immunosurveillance or a separate resident population responsible for local infection control has not been explored. Here, using mice, we show key differences in the migration and tissue localization of memory CD4 + and CD8 + T cells following infection of the skin by herpes simplex virus. On resolution of infection, the skin contained two distinct virus-specific memory subsets; a slow-moving population of sequestered CD8 + T cells that were resident in the epidermis and confined largely to the original site of infection, and a dynamic population of CD4 + T cells that trafficked rapidly through the dermis as part of a wider recirculation pattern. Unique homing-molecule expression by recirculating CD4 + T effector-memory cells mirrored their preferential skin-migratory capacity. Overall, these results identify a complexity in memory T-cell migration, illuminating previously unappreciated differences between the CD4 + and CD8 + subsets.