Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge.
Memory CD8(+) T cells in the lung airways provide protection from secondary respiratory virus challenge by limiting early viral replication. Here, we demonstrate that although airway-resident memory CD8(+) T cells were poorly cytolytic, memory CD8(+) T cells recruited to the airways early during a recall response showed markedly enhanced cytolytic ability. This enhanced lytic activity did not require cognate antigen stimulation, but rather was dependent on STAT1 transcription factor signaling through the interferon-alpha receptor (Ifnar1), resulting in the antigen-independent expression of granzyme B protein in both murine and human virus-specific T cells. Signaling through Ifnar1 was required for the enhanced lytic activity and control of early viral replication by memory CD8(+) T cells in the lung airways. These findings demonstrate that innate inflammatory signals act directly on memory T cells, enabling them to rapidly destroy infected host cells once they enter infected tissues.
Kohlmeier
Jacob E
JE
Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA. jkohlmeier@trudeauinstitute.org
Cookenham
Tres
T
Roberts
Alan D
AD
Miller
Shannon C
SC
Woodland
David L
DL
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011828:Radiation Chimera; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology; D010253:Respirovirus Infections / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D029082:Sendai virus / Q000472:pathogenicity / Q000502:physiology*; D015398:Signal Transduction; D014779:Virus Replication
D000956:Antigens, Viral; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; D053633:Receptor, Interferon alpha-beta; D053804:Granzymes