Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns
| Autor: | Ellen A. Robey, Arthur Weiss, Heather J. Melichar, Jenny O. Ross, Paul Herzmark, Byron B. Au-Yeung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Knockout Clonal Selection thymic slice Thymus Gland Biology CD8-Positive T-Lymphocytes Calcium in biology two photon microscopy Vaccine Related Mice Cell Movement Biodefense Internal medicine MHC class I medicine Cytotoxic T cell Animals Calcium Signaling Receptor Clonal Selection Antigen-Mediated Calcium signaling Mice Knockout Multidisciplinary Prevention ZAP70 T-cell receptor Zap70 Antigen-Mediated Cell biology Emerging Infectious Diseases Endocrinology PNAS Plus biology.protein CD8 |
| Zdroj: | Ross, JO; Melichar, HJ; Au-Yeung, BB; Herzmark, P; Weiss, A; & Robey, EA. (2014). Distinct phases in the positive selection of CD8+T cells distinguished by intrathymic migration and T-cell receptor signaling patterns. Proceedings of the National Academy of Sciences of the United States of America, 111(25). doi: 10.1073/pnas.1408482111. UCSF: Retrieved from: http://www.escholarship.org/uc/item/8062w4x0 Proceedings of the National Academy of Sciences of the United States of America, vol 111, iss 25 |
| DOI: | 10.1073/pnas.1408482111. |
| Popis: | Positive selection of CD8 T cells in the thymus is thought to be a multistep process lasting 3-4 d; however, the discrete steps involved are poorly understood. Here, we examine phenotypic changes, calcium signaling, and intrathymic migration in a synchronized cohort of MHC class I-specific thymocytes undergoing positive selection in situ. Transient elevations in intracellular calcium concentration ([Ca(2+)]i) and migratory pauses occurred throughout the first 24 h of positive selection, becoming progressively briefer and accompanied by a gradual shift in basal [Ca(2+)]i over time. Changes in chemokine-receptor expression and relocalization from the cortex to medulla occurred between 12 and 24 h after the initial encounter with positive-selecting ligands, a time frame at which the majority of thymocytes retain CD4 and CD8 expression and still require T-cell receptor (TCR) signaling to efficiently complete positive selection. Our results identify distinct phases in the positive selection of MHC class I-specific thymocytes that are distinguished by their TCR-signaling pattern and intrathymic location and provide a framework for understanding the multistep process of positive selection in the thymus. |
| Databáze: | OpenAIRE |
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