التفاصيل البيبلوغرافية
| العنوان: |
Islet‐specific CD8+ T cells gain effector function in the gut lymphoid tissues via bystander activation not molecular mimicry. |
| المؤلفون: |
Okada, Mirei, Zhang, Vivian, Loaiza Naranjo, Jeniffer D, Tillett, Bree J, Wong, F Susan, Steptoe, Raymond J, Bergot, Anne‐Sophie, Hamilton‐Williams, Emma E |
| المصدر: |
Immunology & Cell Biology; Jan2023, Vol. 101 Issue 1, p36-48, 13p |
| مصطلحات موضوعية: |
ISLANDS of Langerhans, MOLECULAR mimicry, LYMPHOID tissue, IMMUNE response, T cells, TYPE 1 diabetes, PANCREATIC beta cells |
| مستخلص: |
Type 1 diabetes (T1D) is caused by aberrant activation of autoreactive T cells specific for the islet beta cells. How islet‐specific T cells evade tolerance to become effector T cells is unknown, but it is believed that an altered gut microbiota plays a role. Possible mechanisms include bystander activation of autoreactive T cells in the gut or "molecular mimicry" from cross‐reactivity between gut microbiota‐derived peptides and islet‐derived epitopes. To investigate these mechanisms, we use two islet‐specific CD8+ T cell clones and the non‐obese diabetic mouse model of type 1 diabetes. Both insulin‐specific G9C8 cells and IGRP‐specific 8.3 cells underwent early activation and proliferation in the pancreatic draining lymph nodes but not in the Peyer's patches or mesenteric lymph nodes. Mutation of the endogenous epitope for G9C8 cells abolished their CD69 upregulation and proliferation, ruling out G9C8 cell activation by a gut microbiota derived peptide and molecular mimicry. However, previously activated islet‐specific effector memory cells but not naïve cells migrated into the Peyer's patches where they increased their cytotoxic function. Oral delivery of butyrate, a microbiota derived anti‐inflammatory metabolite, reduced IGRP‐specific cytotoxic function. Thus, while initial activation of islet‐specific CD8+ T cells occurred in the pancreatic lymph nodes, activated cells trafficked through the gut lymphoid tissues where they gained additional effector function via non‐specific bystander activation influenced by the gut microbiota. [ABSTRACT FROM AUTHOR] |
|
Copyright of Immunology & Cell Biology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |