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J. D. Lovaas, G. Shi, C. Tan, B. P. Vistica, E. F. Wawrousek, I. Gery; A Subpopulation of Th17 Cells Produce High Levels of IL-17, but Fail to Adoptively Transfer Ocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2640.
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Th17 cells were identified to be highly immunopathogenic in several autoimmune models, including experimental autoimmune uveitis (EAU). More recently, however, the Th17 population was reported by Cua’s group to also include a subset of non-pathogenic cells (McGeachy et al., Nature Immunol, 2007). Here we examined this dichotomy by a system of adoptively transferred ocular inflammation.
Naïve CD4 TCR transgenic cells specific against hen egg lysozyme (HEL) were activated with APC and HEL ("APC/HEL"), or with plate-bound anti-CD3/CD28 antibodies ("PbAb") during polarization with IL-6 and TGF-beta. The cultured cells were tested for production of cytokines, chemokines and chemokine receptors, as well as their capacity to adoptively transfer ocular inflammation in recipient mice expressing HEL in their eyes.
The two culturing procedures yielded populations with similar levels of IL-17 producing cells (~35%) and similar levels of IL-10, but with remarkably different other features: (i) APC/HEL induced ocular inflammation, but PbAb cells did not; (ii) PbAb cells produced higher levels of IL-17 than APC/HEL cells; (iii) APC/HEL cells produced IL-22 at levels higher by far (~ 100 fold) than PbAb cells; (iv) the two sub-populations differed in their expression of chemokines and chemokine receptors, with patterns similar to those reported by Cua’s group.
Our system offers a novel and more simplified method for obtaining the immunopathogenic and non-pathogenic sub-populations of Th17. Unlike in Cua’s system, no pre-activation is necessary and a major difference between the two sub-populations is in the production level of IL-22, not IL-10. Moreover, our new system makes it possible to further dissect the newly described two Th17 sub-populations for features that determine their different biological activities.
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