title: CD8brightCD56+ T cells are cytotoxic effectors in patients with active Behcet's uveitis.
abstract: Behçet's uveitis, characterized by chronic recurrent uveitis and obliterating retinal vasculitis, frequently causes bilateral blindness. Intraocular infiltration of TCRalphabeta+CD8brightCD56+ cells was a distinct feature in Behçet's uveitis. However, phenotypic natures and effector functions of the cells have remained elusive. This study was conducted to determine phenotypic and functional characteristics and cytotoxic mechanisms of CD8brightCD56+ T cells in Behçet's uveitis. CD11b+CD27-CD62L- phenotypes of CD8brightCD56+ T cells were increased in patients with active Behçet's uveitis compared with inactive Behcet's patients and normal controls. Interestingly, CD45RAdimCD45RO- phenotypes were expanded, and CD94 expression was markedly up-regulated in contrast to the down-regulation of NKG2D. Furthermore, these subsets were polarized to produce IFN-gamma and contained high amounts of preformed intracellular perforin while exclusively expressing surface FasL upon PI stimulation. Moreover, the cytolytic functions of freshly isolated CD8brightCD56+ T cells were up-regulated against both K562 (NK-sensitive) and Raji (NK-resistant) cells, which were effectively inhibited by perforin inhibitor (concanamycin A). Their cytolytic activity against HUVECs was also increased and was effectively suppressed by Fas ligand inhibitor (brefeldin A) and partly by perforin inhibitor. Furthermore, cytolytic functions of PMA and ionomycin-stimulated CD8brightCD56+ T cells against HUVECs were greatly enhanced, by pretreatment of recombinant human IFN-gamma on HUVECs. Therefore, CD8brightCD56+ T cells in Behçet's uveitis are characterized by cytotoxic effector phenotypes with functional NK receptors and function as strong cytotoxic effectors through both Fas ligand-dependent and perforin-dependent pathways.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea.
authors.forename: Jae Kyoun
authors.initials: JK
authors.lastname: Ahn
authors.forename: Hum
authors.initials: H
authors.lastname: Chung
authors.forename: Dong-sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Hyeong Gon
authors.initials: HG
authors.lastname: Yu
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology* / Q000473:pathology; D019002:CD56 Antigen / Q000032:analysis*; D016764:Cell Polarity; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D042783:Endothelial Cells / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic / Q000032:analysis; D055607:Receptors, Natural Killer Cell; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000032:analysis
chemical_list: D019002:CD56 Antigen; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C527085:KLRK1 protein, human; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D048069:Tumor Necrosis Factors; D054353:Perforin; D007371:Interferon-gamma