Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance

Jossef F. Osborn, Samuel J. Hobbs, Jana L. Mooster, Tahsin N. Khan, Augustus M. Kilgore, Jake C. Harbour, Jeffrey Nolz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Memory CD8+ T cells in the circulation rapidly infiltrate non-lymphoid tissues following infection and provide protective immunity in an antigen-specific manner. However, the subsequent fate of memory CD8+ T cells after entering non-lymphoid tissues such as the skin during a secondary infection is largely unknown. Furthermore, because expression of CD62L is often used to identify the central memory (TCM) CD8+ T cell subset, uncoupling the physical requirement for CD62L-mediated lymph node homing versus other functional attributes of TCM CD8+ T cells remains unresolved. Here, we show that in contrast to naïve CD8+ T cells, memory CD8+ T cells traffic into the skin independent of CD62L-mediated lymph node re-activation and provide robust protective immunity against Vaccinia virus (VacV) infection. TCM, but not effector memory (TEM), CD8+ T cells differentiated into functional CD69+/CD103- tissue residents following viral clearance, which was also dependent on local recognition of antigen in the skin microenvironment. Finally, we found that memory CD8+ T cells expressed granzyme B after trafficking into the skin and utilized cytolysis to provide protective immunity against VacV infection. Collectively, these findings demonstrate that TCM CD8+ T cells become cytolytic following rapid infiltration of the skin to protect against viral infection and subsequently differentiate into functional CD69+ tissue-residents.

Original languageEnglish (US)
Pages (from-to)e1007633
JournalPLoS pathogens
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2019

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Virus Diseases
Lymph Nodes
T-Lymphocytes
Skin
Immunity
Vaccinia virus
Antigens
Granzymes
T-Lymphocyte Subsets
Coinfection
Infection

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance. / Osborn, Jossef F.; Hobbs, Samuel J.; Mooster, Jana L.; Khan, Tahsin N.; Kilgore, Augustus M.; Harbour, Jake C.; Nolz, Jeffrey.

In: PLoS pathogens, Vol. 15, No. 3, 01.03.2019, p. e1007633.

Research output: Contribution to journalArticle

Osborn, Jossef F. ; Hobbs, Samuel J. ; Mooster, Jana L. ; Khan, Tahsin N. ; Kilgore, Augustus M. ; Harbour, Jake C. ; Nolz, Jeffrey. / Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance. In: PLoS pathogens. 2019 ; Vol. 15, No. 3. pp. e1007633.
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