NK cells require antigen-specific memory CD4+ T cells to mediate superior effector functions during HSV-2 recall responses in vitro. Issue 4 (14th December 2016)

• Record Type: Journal Article
• Authors: Chen, Branson; Lee, Amanda J; Chew, Marianne V; Ashkar, Ali A
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 4(2017)
• Page Start: 1045
• Page End: 1052
• Publication Date: 2016-12-14
• Subjects: interferon γ -- innate immunity -- adaptive immunity; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0416-192R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Cross-talk between HSV-2-specific CD4 + T cell and NK cells impacts NK cell function during secondary exposure to HSV-2 antigens. 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