Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 22Brian K. Chung 1 , Lenka L. Allan, John J. Priatel, Peter van den Elzen andRusung TanDepartment of Pathology & Laboratory Medicine, University of British Columbia and BCChildren’s Hospital, Vancouver, BCBrian K. Chungnatural killer t cells kill epstein-barr virustransformed b cells following cd1d upregulation byretinoic acid receptor-alphaBackround/ObjectivesNatural killer T (NKT) cells are innate-like lymphocytes that recognize lipid antigens presented by highly conservedCD1d molecules. Individuals lacking NKT cells, such as patients with X-linked lymphoproliferative disease developsevere and often fatal lymphoproliferative disorders following Epstein-Barr virus (EBV) infection. Here, we show thatEBV transformation of naïve human tonsillar B cells into lymphoblastoid cell lines (LCL) induces downregulation ofsurface CD1d but not MHC class I or MHC class II. Unlike naïve B cells, tonsillar LCL loaded with the exogenousNKT cell agonist alpha-galactosylceramide (alpha-GalCer) fail to activate NKT cells. To determine whether CD1ddependentactivation of NKT cells could be restored, LCL were treated with the synthetic retinoic acid receptor-alpha(RAR-alpha) agonist AM580 known to upregulate CD1d. Treatment with AM580 elevated transcriptional andsurface expression of CD1d in LCL rendering them capable of stimulating IFN-gamma secretion and cytotoxicityby NKT cells, even in the absence of exogenous lipid agonists. When AM580-treated LCL were pulsed with alpha-GalCer, NKT cell effector functions were further enhanced. These results argue that EBV transformed B cells mayevade NKT cell surveillance in vivo by downregulating CD1d expression and suggest that AM580 and alpha-GalCermay be used synergistically to augment NKT cell function.32 2 0 1 0 * O r a l P r e s e n t a t i o n s