title: NK cells require antigen-specific memory CD4+T cells to mediate superior effector functions during HSV-2 recall responses in vitro.
abstract: Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV-2) infections. However their role as effectors in adaptive immune responses against HSV-2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN-γ) upon re-exposure to HSV-2 antigens in a mouse model of genital HSV-2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN-γ. Our results demonstrate that HSV-2-experienced CD4+T cells have a crucial role in coordinating NK cell activation and that their presence during HSV-2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell-to-cell contacts for both CD4+T cells and NK cells. NK cells are dependent on direct interactions with other HSV-2-experienced splenocytes, and CD4+T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV-2 antigens and, in fact, require specific interactions with HSV-2-experienced CD4+T cells to produce IFN-γ.
authors.affiliation: Department of Pathology and Molecular Medicine, Institute of Infectious Disease Research and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Branson
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pathology and Molecular Medicine, Institute of Infectious Disease Research and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Pathology and Molecular Medicine, Institute of Infectious Disease Research and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Chew
authors.affiliation: Department of Pathology and Molecular Medicine, Institute of Infectious Disease Research and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada ashkara@mcmaster.ca.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology
chemical_list: D000956:Antigens, Viral; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: adaptive immunity; innate immunity; interferon γ