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• Natural killer T cells in chronic uveitis
  Jae Kyoun Ahn
  Published on: 19 October 2007

• Published on: 19 October 2007

  Natural killer T cells in chronic uveitis

  • Jae Kyoun Ahn, Assistant Professor
  • Other Contributors:
    • Yeoung G. Park, Kyung C. Yoon

  Dear Editor

  I read with interest the article by Pedroza-Seres M and associates who assessed the pathogenic roles of peripheral CD57+ natural killer T (NKT) cell in pars planitis.[1] The authors compared the frequencies of CD57+ NKT cell in peripheral blood between pars planitis patients and healthy controls, and then evaluated the effector-related surface molecules and functions of CD57+ NKT cells derived from pa...

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  Dear Editor

  I read with interest the article by Pedroza-Seres M and associates who assessed the pathogenic roles of peripheral CD57+ natural killer T (NKT) cell in pars planitis.[1] The authors compared the frequencies of CD57+ NKT cell in peripheral blood between pars planitis patients and healthy controls, and then evaluated the effector-related surface molecules and functions of CD57+ NKT cells derived from patients. The authors conclude that CD57+ NKT cell subsets may function as memory-effector T cells during pars planitis immunopathogenesis. My experience of using similar methods to investigate the phenotypes and functions of CD8^brightCD56+ T cells in Behçet uveitis supports the notion that NK-typed CD8+ T cells play an effector role in chronic uveitis.[2] I would like to offer my opinion to their interpretation of experimental results.

  I observed that CD8^bright CD56+ cells in peripheral blood were composed of more than 95% TCRαβ cells and that CD8^dimCD56+ cells consisted of natural killer cells and γδTCR+ cells.[2,3] Because the authors used the different gate of CD8 expression in figure 1 and 3, it is possible to overestimate the frequencies of peripheral CD8+CD57+ T cells including CD8^dim populations. Likewise CD56+ cells, CD8^dimCD57+ cells may not be TCRαβcells, which require confirmation of TCR expression. As shown in Figure 4 and Table 3, the authors found that CD57+CD8+ T cells significantly produced IL-4 after nonspecific stimulation. However, these results are not compatible with the idea that terminally differentiated NK-typed CD8+ T cells are polarized to produce cytokines, like CD56+CD8+ T cells.[2] Apoptosis of ex vivo CD57+CD8+ T cells may contribute to these findings because of smaller cell counts after stimulation (thick lines). The authors described that stimulared or unstimulated immune cells were used for intracellular staining of perforin. Because CD8+CD56+ T cells shed the preformed intracellular perforin after in vitro stimulation, the authors should measure the amounts of intracellular perforin in unstimulated cells.

  I agree with the authors that NK-typed CD8+ T cells exert potent effector functions over conventional CD8+ T cells. CD56+ T cells are recruited into eye, particularly in Behçet uveitis, which are different from other etiologies of uveitis.[3] Moreover, these cells show phenotypical or functional changes after immunosuppresive treatments.[4] However, I did not observe upregulation of CD56+ T cells in aqueous or peripheral blood in patients with intermediate uveitis.[3] The specific roles of CD57+CD8+ T cells in pars planitis pathogenesis are not definite because the authors did not evaluate phenotypical or functional differences of CD57+CD8+ T cells according to the disease activity or compare their results with other etiologies of uveitis. Therefore, further investigations are needed to identify the pathogenic roles of CD57+CD8+ T cells in pars planitis.

  References

  1. Pedroza-Seres M, Linares M, Voorduin S, et al. Pars planitis is associated with an increased frequency of effector-memory CD57+ T cells. Br J Ophthalmol 2007;91:1393-8.

  2. Ahn JK, Chung H, Lee DS, Yu YS, Yu HG. CD8^brightCD56+ T cells are cytotoxic effectors in patients with active Behçet's uveitis. J Immunol 2005;175:6133-42.

  3. Yu HG, Lee DS, Seo JM, et al. The number of CD8+ T cells and NKT cells increases in the aqueous humor of patients with Behçet's uveitis. Clin Exp Immunol 2004;137:437-43.

  4. Ahn JK, Park YG, Park SW, et al. Combined low dose cyclosporine and prednisone down-regulate natural killer cell-like effector functions of CD8^brightCD56+ T cells in patients with active Behçet's uveitis. Ocul Immunol Inflamm 2006;14:267-275.

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  Conflict of Interest:
  None declared.

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