CD8brightCD56+ T cells are cytotoxic effectors in patients with active Behcet's uveitis

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Ahn, Jae Kyoun; Chung, Hum; Lee, Dong-sup; Yu, Young Suk; Yu, Hyeong Gon
Issue Date
American Association of Immunologists
J Immunol. 2005 Nov 1;175(9):6133-42.
AdultAntigens, CD56/*analysisBehcet Syndrome/*immunology/pathologyCell PolarityCells, CulturedCytotoxicity, ImmunologicEndothelial Cells/pathologyFas Ligand ProteinFemaleHumansInterferon-gamma/biosynthesis/pharmacologyMaleMembrane Glycoproteins/analysisMiddle AgedNK Cell Lectin-Like Receptor Subfamily KPerforinPore Forming Cytotoxic ProteinsReceptors, Immunologic/analysisReceptors, Natural Killer CellT-Lymphocytes, Cytotoxic/*immunologyTumor Necrosis Factors/analysis
Behcet'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 Behcet'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 Behcet's uveitis. CD11b+CD27-CD62L- phenotypes of CD8brightCD56+ T cells were increased in patients with active Behcet'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 Behcet'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.
0022-1767 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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