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 nodes¹, resulting in memory T cells that provide local and systemic protection². 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 body³. However, T-cell immunity consists of separate CD4⁺ helper T cells and CD8⁺ killer T cells, with distinct effector and memory programming requirements⁴. 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.