Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection

Abstract

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.

Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

“…Recent work also demonstrates that the quality of functional CD8 T RM responses in the influenza-infected lung is dependent on the type of cell presenting viral antigens ( 100 ). Furthermore, T RM can also egress from tissues, convert into other memory subsets, and change their migratory behavior depending on the inflammatory context ( 101 , 102 ). Together these findings contribute to an increasingly multidimensional view of the factors that drive T RM formation, what constitutes tissue residence, and the role T RM play in antiviral defense.…”

Adaptive immunity to human coronaviruses is widespread but low in magnitude

“…24,25 Furthermore, data comparing hCoV-specific T-or Bcell responses in the circulation with the presence or absence of such responses in the respiratory tract or secondary lymphoid organs (SLO) are lacking. Studies in animal models suggest that respiratory infections can generate long-lived T-cell memory in lung-draining lymph nodes (LDLN), 28 raising the possibility of analogous responses following hCoV infection.…”

IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection

“…T EX are not conventional memory T cells, but rather are comprised of transcriptionally and phenotypically distinct subsets organized in an intricate precursor–progeny relationship [ 19 , 20 ]. Note that there are exceptions to these working memory subset designations, such as recent evidence that T RM can leave tissues and migrate to draining lymph nodes where they can transmogrify into T CM and reenter the circulation [ 21 , 22 , 23 ].…”