title: Different patterns of peripheral migration by memory CD4+ and CD8+ T cells.
abstract: 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, resulting in memory T cells that provide local and systemic protection. 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. However, T-cell immunity consists of separate CD4(+) helper T cells and CD8(+) killer T cells, with distinct effector and memory programming requirements. 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.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria 3010, Australia. gebhardt@unimelb.edu.au
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.forename: Ali
authors.initials: A
authors.lastname: Zaid
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mackay
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement; D019040:E-Selectin / Q000378:metabolism; D018392:Genomic Imprinting; D006561:Herpes Simplex / Q000276:immunology / Q000821:virology; D007156:Immunologic Memory; D007157:Immunologic Surveillance / Q000276:immunology; D008024:Ligands; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D018139:Simplexvirus / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin