The Plasticity and Stability of Regulatory T Cells during Viral-Induced Inflammatory Lesions.
| Autor: | Bhela S; Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996., Varanasi SK; Department of Genome Science and Technology, University of Tennessee, Knoxville, TN 37996; and., Jaggi U; Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996., Sloan SS; Department of Microbiology, University of Tennessee, Knoxville, TN 37996., Rajasagi NK; Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996., Rouse BT; Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996; btr@utk.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Aug 15; Vol. 199 (4), pp. 1342-1352. Date of Electronic Publication: 2017 Jul 14. |
| DOI: | 10.4049/jimmunol.1700520 |
| Abstrakt: | Ocular infection with HSV causes a chronic T cell-mediated inflammatory lesion in the cornea. Lesion severity is affected by the balance of different CD4 T cell subsets, with greater severity occurring when the activity of regulatory T cells (Tregs) is compromised. In this study, fate-mapping mice were used to assess the stability of Treg function in ocular lesions. We show that cells that were once Foxp3 + functional Tregs may lose Foxp3 and become Th1 cells that could contribute to lesion expression. The instability primarily occurred with IL-2R lo Tregs and was shown, in part, to be the consequence of exposure to IL-12. Lastly, in vitro-generated induced Tregs (iTregs) were shown to be highly plastic and capable of inducing stromal keratitis when adoptively transferred into Rag1 -/- mice, with 95% of iTregs converting into ex-Tregs in the cornea. This plasticity of iTregs could be prevented when they were generated in the presence of vitamin C and retinoic acid. Importantly, adoptive transfer of these stabilized iTregs to HSV-1-infected mice prevented the development of stromal keratitis lesions more effectively than did control iTregs. Our results demonstrate that CD25 lo Treg and iTreg instability occurs during a viral immunoinflammatory lesion and that its control may help to avoid lesion chronicity. (Copyright © 2017 by The American Association of Immunologists, Inc.) |
| Databáze: | MEDLINE |
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