title: Innate immune control of EBV-infected B cells by invariant natural killer T cells.
abstract: Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-α agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon γ secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition.
authors: Child and Family Research Institute, Immunity in Health and Disease, and Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Children's Hospital, Vancouver, BC, Canada; and.
authors: Brian K
authors: BK
authors: Chung
authors: Kevin
authors: K
authors: Tsai
authors: Lenka L
authors: LL
authors: Allan
authors: Dong Jun
authors: DJ
authors: Zheng
authors: Johnny C
authors: JC
authors: Nie
authors: Catherine M
authors: CM
authors: Biggs
authors: Mohammad R
authors: MR
authors: Hasan
authors: Frederick K
authors: FK
authors: Kozak
authors: Peter
authors: P
authors: van den Elzen
authors: John J
authors: JJ
authors: Priatel
authors: Rusung
authors: R
authors: Tan
mesh_terms: D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002450:Cell Communication / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000276:immunology / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000821:virology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1