Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory

Abstract

CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8+ resident memory T cells (TRM cells) within the reproductive tracts of live female mice. We found that mucosal TRM cells were highly motile, but paused and underwent in situ division after local antigen challenge. TRM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent TRM cell differentiation in situ. However, the proliferation of pre-existing TRM cells dominated the local mucosal recall response and contributed most substantially to the boosted secondary TRM cell population. We observed similar results in skin. Thus, TRM cells can autonomously regulate the expansion of local immunosurveillance independently of central memory or proliferation in lymphoid tissue.

Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity

“…Of note, based on published data indicating that 3°M cells proliferate less than naive CD8 T cells in response to systemic infection (Wirth et al, 2010) and in order to achieve similar frequencies of circulating 1°M and 4°M P14 cells, mice received 10 5 3°M P14 cells. This model not only permitted isolation and transfer of P14 cells with a known antigen exposure history but also incorporated the recently established notion that circulating memory T cells can be recruited to tissues and generate T rm after repeated infections (Beura et al, 2018; Park et al, 2018). Figure S1A depicts selected phenotypic characteristics of naive and 3M spleenderived P14 which were the precursors of 1M and 4M lung T rm .…”

“…Instead, we build on recent data describing the capacity of circulating memory CD8 + T cells to be recruited to the site of infection and convert to T rm (Beura et al, 2018; Park et al, 2018). Thus, we describe fundamental differences between T rm populations that were established by recruitment from the pool of circulating CD8 + T cells that were exposed to influenza lung infections once or multiple times, in an otherwise naive host.…”

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…Thus, in addition to a sentinel system, mucosal T RM function as a robust self-sufficient defense system and can function independent of circulating T cells. 104,107 …”

Herpes simplex virus‐2 dynamics as a probe to measure the extremely rapid and spatially localized tissue‐resident T‐cell response

“…The rarity of T RM recirculation was established in parabiosis studies, in which the circulatory systems of 2 mice are joined to allow even mixing of circulating T cells: tellingly, T cells in peripheral tissues equilibrate to a much lesser extent due to their lack of recirculation . Labeling experiments demonstrate that persistence of this population does not depend on contribution from circulating T cells . In humans, donor tissue‐resident T cells with tissue‐resident markers were noted in a biopsy following a facial transplantation; these results replicated similar results in murine tissue‐graft experiments .…”