1. NK cells require antigen-specific memory CD4 + T cells to mediate superior effector functions during HSV-2 recall responses in vitro.
- Author
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Chen B, Lee AJ, Chew MV, and Ashkar AA
- Subjects
- Animals, Female, Immunization, Interferon-gamma biosynthesis, Interleukin-2 metabolism, Killer Cells, Natural cytology, Lymphocyte Activation, Mice, Inbred C57BL, Spleen cytology, Antigens, Viral immunology, CD4-Positive T-Lymphocytes immunology, Herpesvirus 2, Human immunology, Immunologic Memory, Killer Cells, Natural immunology
- 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., (© Society for Leukocyte Biology.)- Published
- 2017
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