T cells generated in the absence of a thoracic thymus fail to establish homeostasis |
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| Authors: | Christa Smolarchuk Lin Fu Zhu William F. N. Chan Colin C. Anderson |
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| Affiliation: | 1. Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada;2. Department of Surgery, University of Alberta, Edmonton, AB, Canada;3. Alberta Diabetes and Transplant Institutes, University of Alberta, Edmonton, AB, Canada |
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| Abstract: | Cervical thymus mimics the thoracic thymus in supporting T‐cell development and exists in a subset of mice and humans. Importantly, it remains unknown whether the cervical thymus can generate T cells that are self‐tolerant in the complete absence of signals from the thoracic thymus. Using a fetal liver reconstitution model in thoracic thymectomized RAG?/? mice, we found that T cells could be generated without contribution from the thoracic thymus. However, these mice had decreased T cells, increased proportions of effector memory T cells and Treg phenotype cells, increased serum IgG1/2b, and increased frequency of T cells expressing IFN‐γ, IL‐17 or IL‐10. Half of the mice that received a thoracic thymectomy and fetal liver cells, unlike sham surgery controls, developed substantial morbidity with age. Disease was associated with lymphopenia‐driven activation rather than inherent defects in the cervical thymus, as both thoracic and cervical thymocytes could generate disease in lymphopenic recipients. Administration of the homeostatic cytokine IL‐7 caused a rapid, transient increase in T‐cell numbers and reduced the time to disease onset. Together the data suggests that the cervical thymus can function in the complete absence of the thoracic thymus; however, the T cells generated do not establish homeostasis. |
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| Keywords: | Autoimmunity Homeostasis Lymphopenia Regulatory T cells Thymopoiesis |
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