Innate immunity defines the capacity of antiviral T cells to limit persistent infection.
Effective immunity requires the coordinated activation of innate and adaptive immune responses. Natural killer (NK) cells are central innate immune effectors, but can also affect the generation of acquired immune responses to viruses and malignancies. How NK cells influence the efficacy of adaptive immunity, however, is poorly understood. Here, we show that NK cells negatively regulate the duration and effectiveness of virus-specific CD4+ and CD8+ T cell responses by limiting exposure of T cells to infected antigen-presenting cells. This impacts the quality of T cell responses and the ability to limit viral persistence. Our studies provide unexpected insights into novel interplays between innate and adaptive immune effectors, and define the critical requirements for efficient control of viral persistence.
Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University Department of Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia.
Daniel M
DM
Andrews
Marie J
MJ
Estcourt
Christopher E
CE
Andoniou
Matthew E
ME
Wikstrom
Andrea
A
Khong
Valentina
V
Voigt
Peter
P
Fleming
Hyacinth
H
Tabarias
Geoffrey R
GR
Hill
Robbert G
RG
van der Most
Anthony A
AA
Scalzo
Mark J
MJ
Smyth
Mariapia A
MA
Degli-Esposti
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D000939:Epitopes; D006649:Histocompatibility Antigens / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000172:deficiency / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D000998:Antiviral Agents; D000939:Epitopes; D006649:Histocompatibility Antigens; D055650:NK Cell Lectin-Like Receptor Subfamily A; D010455:Peptides