Open AccessRetrograde migration supplies resident memory T cells to lung-draining LN after influenza infection
Author(s) -
J. Michael Stolley,
Timothy S. Johnston,
Andrew G. Soerens,
Lalit K. Beura,
Pamela C. Rosato,
Vineet Joag,
Sathi Wijeyesinghe,
Ryan A. Langlois,
Kevin C. Osum,
Jason S. Mitchell,
David Masopust
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20192197
Subject(s) - lung , cd8 , biology , antigen , immunology , lymphatic system , phenotype , cytotoxic t cell , granzyme b , medicine , genetics , gene , in vitro
Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate that contraction of lung CD8+ T cell responses after influenza infection is contemporized with egress of CD69+/CD103+ CD8+ T cells to the draining mediastinal LN via the lymphatic vessels, which we term retrograde migration. Cells within the draining LN retained canonical markers of lung TRM, including CD103 and CD69, lacked Ly6C expression (also a feature of lung TRM), maintained granzyme B expression, and did not equilibrate among immunized parabiotic mice. Investigations of bystander infection or removal of the TCR from established memory cells revealed that the induction of the TRM phenotype was dependent on antigen recognition; however, maintenance was independent. Thus, local lung infection induces CD8+ T cells with a TRM phenotype that nevertheless undergo retrograde migration, yet remain durably committed to the residency program within the draining LN, where they provide longer-lived regional memory while chronicling previous upstream antigen experiences.