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CD8^brightCD56⁺ T Cells Are Cytotoxic Effectors in Patients with Active Behçet’s Uveitis¹

Jae Kyoun Ahn^2,*, Hum Chung^2,*, Dong-sup Lee, Young Suk Yu^* and Hyeong Gon Yu^3,*

^* Department of Ophthalmology, Seoul National University College of Medicine, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea; and Department of Anatomy, Seoul National University Hospital Cancer Research Institute, Seoul, Korea

Behçet’s uveitis, characterized by chronic recurrent uveitis and obliterating retinal vasculitis, frequently causes bilateral blindness. Intraocular infiltration of TCR⁺CD8^brightCD56⁺ 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 CD8^brightCD56⁺ T cells in Behçet’s uveitis. CD11b⁺CD27^–CD62L^– phenotypes of CD8^brightCD56⁺ T cells were increased in patients with active Behçet’s uveitis compared with inactive Behcet’s patients and normal controls. Interestingly, CD45RA^dimCD45RO^– 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- and contained high amounts of preformed intracellular perforin while exclusively expressing surface FasL upon PI stimulation. Moreover, the cytolytic functions of freshly isolated CD8^brightCD56⁺ 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 CD8^brightCD56⁺ T cells against HUVECs were greatly enhanced, by pretreatment of recombinant human IFN- on HUVECs. Therefore, CD8^brightCD56⁺ 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.

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