Persistence of IL-2 expressing Th17 cells in healthy humans and experimental autoimmune uveitis

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Title
Persistence of IL-2 expressing Th17 cells in healthy humans and experimental autoimmune uveitis
Author(s)
C R Yu; Hyun Mee Oh; N Golestaneh; A Amadi-Obi; Y S Lee; A Eseonu; R M Mahdi; C E Egwuagu
Bibliographic Citation
European Journal of Immunology, vol. 41, no. 12, pp. 3495-3505
Publication Year
2011
Abstract
Compared with other T-helper subsets, Th17 cell numbers are very low in human blood but become elevated in chronic inflammatory diseases. In this study, we investigated mechanisms that may explain the frequent involvement of Th17 cells in autoimmune diseases such as uveitis. We compared Th17 and Th1 subsets and found that Th17 cells expressed lower IL-2 levels during Ag-priming and this correlated with their decreased susceptibility to activation-induced cell death (AICD). However, complete depletion of IL-2 with IL-2 neutralizing antibodies rendered Th17 cells as susceptible to apoptosis as Th1 cells, suggesting that the low levels of IL-2 produced by Th17 cells conferred survival advantages to this subset. We describe here a Th17 subtype that constitutively produces very low levels of IL-2 (Th17-DP). The Th17-DP population increased dramatically in the blood and retina of mice during experimental autoimmune uveitis, indicating their potential involvement in the etiology of uveitis. We further show that the majority of the memory Th17 cells in human blood are Th17-DP and are targets of daclizumab, an IL-2R antibody used in treating recalcitrant uveitis. Thus, Th17 cells may persist in tissues and contribute to chronic inflammation by limiting IL-2 production to levels that cannot provoke IL-2-induced AICD yet are sufficient to promote Th17 homeostatic expansion.
Keyword
Animal modelsAutoimmunityClinical immunologyInflammationT helper cells
ISSN
0014-2980
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/eji.201141654
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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