Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus.
Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV.
Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Bram
B
Slütter
Lecia L
LL
Pewe
Susan M
SM
Kaech
John T
JT
Harty
D019264:Adoptive Transfer; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology; D007117:Immunization, Secondary; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000276:immunology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D014611:Vaccination
C515188:Cxcr3 protein, mouse; C508032:Ifnar1 protein, mouse; D007252:Influenza Vaccines; D054367:Receptors, CXCR3; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12