Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.
Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity.
Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Jason T
JT
White
Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Eric W
EW
Cross
Department of Medicine and Division of Gastroenterology and Hepatology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Matthew A
MA
Burchill
Department of Biomedical Research, National Jewish Health, Denver, Colorado 80206, USA.
Thomas
http://orcid.org/0000-0002-3861-8602
T
Danhorn
Department of Surgery, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Martin D
MD
McCarter
Department of Medicine and Division of Gastroenterology and Hepatology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Hugo R
HR
Rosen
Department of Biomedical Research, National Jewish Health, Denver, Colorado 80206, USA.
Brian
B
O'Connor
Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Ross M
RM
Kedl
D000328:Adult; D000368:Aged; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D001324:Autoantigens; D019409:Interleukin-15