The Plasticity and Stability of Regulatory T Cells during Viral-Induced Inflammatory Lesions
| Autor: | Sarah S. Sloan, Naveen K. Rajasagi, Barry T. Rouse, Ujjaldeep Jaggi, Siddheshvar Bhela, Siva Karthik Varanasi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Adoptive cell transfer Cellular differentiation Immunology Cell Plasticity Retinoic acid chemical and pharmacologic phenomena Tretinoin Ascorbic Acid Herpesvirus 1 Human Biology Lymphocyte Activation T-Lymphocytes Regulatory Article Lesion Cornea 03 medical and health sciences chemistry.chemical_compound Mice T-Lymphocyte Subsets medicine Immunology and Allergy Animals Homeodomain Proteins Interleukin-2 Receptor alpha Subunit FOXP3 hemic and immune systems Cell Differentiation Forkhead Transcription Factors Th1 Cells Ascorbic acid Adoptive Transfer Interleukin-12 030104 developmental biology chemistry Interleukin 12 Keratitis Herpetic Female medicine.symptom medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 199(4) |
| ISSN: | 1550-6606 |
| Popis: | 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-2Rlo 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 CD25lo Treg and iTreg instability occurs during a viral immunoinflammatory lesion and that its control may help to avoid lesion chronicity. |
| Databáze: | OpenAIRE |
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