title: Bidirectional NK/DC interactions promote CD4 expression on NK cells, DC maturation, and HIV infection.
abstract: Interactions between natural killer (NK) and dendritic cells (DCs) are integral to immune response development, potentially leading to bidirectional NK/DC activation. We demonstrate that autologous NK/DC interactions induce CD4 expression on NK cells, influencing degranulation. Cell contact is required, with high NK:DC ratios and mature DCs most effectively inducing CD4 expression. CD4(+) NK cells, in turn, mediate DC maturation via contact-dependent and independent pathways, more effectively maturing DCs than CD4(-) NK cells. Bidirectional NK/DC interactions also impact HIV infection, as NK-matured DCs effectively deliver infectious HIV to T cells, via trans-infection. DC-induced CD4 expression also renders NK cells susceptible to HIV infection. Focusing on NK/DC interactions, DCs can transfer infectious virus and enhance HIV infection of CD4(+) NK cells, strongly suggesting that these interactions influence HIV pathogenesis. Findings provide new insight regarding NK/DC interactions, defining a mechanism by which cellular interactions in the absence of pathogens promote DC-mediated amplification of HIV infection.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Valentin-Torres
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ramirez Kitchen
authors.forename: Harold S
authors.initials: HS
authors.lastname: Haller
authors.forename: Helene B
authors.initials: HB
authors.lastname: Bernstein
mesh_terms: D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D015550:Cell Degranulation / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens