Skin infection generates non-migratory memory CD81 TRM cells providing global skin immunity

Skin infection generates non-migratory memory CD81 TRM cells providing global skin immunity

Skin infection generates non-migratory memory CD81 TRM cells providing global skin immunity

Abstract

Protective T-cell memory has long been thought to reside in blood
and lymph nodes, but recently the concept of immune memory in
peripheral tissues mediated by resident memory T (TRM) cells has
been proposed1–5. Here we show in mice that localized vaccinia
virus (VACV) skin infection generates long-lived non-recirculating
CD81 skin TRM cells that reside within the entire skin. These skin
TRM cells are potent effector cells, and are superior to circulating
central memory T (TCM) cells at providing rapid long-term protection
against cutaneous re-infection. We find that CD81 T cells
are rapidly recruited to skin after acute VACV infection. CD81
T-cell recruitment to skin is independent of CD41 T cells and
interferon-c, but requires the expression of E- and P-selectin ligands
by CD81 T cells. Using parabiotic mice, we further show that
circulating CD81 TCM and CD81 skin TRM cells are both generated
after skin infection; however, CD81 TCM cells recirculate between
blood and lymph nodes whereas TRM cells remain in the skin.
Cutaneous CD81 TRM cells produce effector cytokines and persist
for at least 6 months after infection. Mice with CD81 skin TRM cells
rapidly cleared a subsequent re-infection with VACV whereas mice
with circulating TCM but no skin TRM cells showed greatly impaired
viral clearance, indicating that TRM cells provide superior protection.
Finally, we showthatTRMcells generated as a result of localized
VACVskin infection reside not only in the site of infection, but also
populate the entire skin surface and remain present for many
months. Repeated re-infections lead to progressive accumulation
of highly protective TRM cells in non-involved skin. These findings
have important implications for our understanding of protective
immune memory at epithelial interfaces with the environment, and
suggest novel strategies for vaccines that protect against tissue
tropic organisms.

 

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