Inflammation and TCR signal strength determine the breadth of the T cell response in a bim-dependent manner
| Autor: | Martin Prlic, Michael J. Bevan, Dietmar Zehn, Sarah Roepke, Kristin Weakly |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
T cell
Immunology Receptors Antigen T-Cell Mice Transgenic Streptamer Biology CD8-Positive T-Lymphocytes Article 03 medical and health sciences Mice 0302 clinical medicine T-Lymphocyte Subsets Proto-Oncogene Proteins medicine Immunology and Allergy Cytotoxic T cell Animals Antigen-presenting cell 030304 developmental biology Inflammation 0303 health sciences Bcl-2-Like Protein 11 Cell Death T-cell receptor CD28 Membrane Proteins 3. Good health Cell biology medicine.anatomical_structure Apoptosis Regulatory Proteins Memory T cell Immunologic Memory CD8 030215 immunology Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore Md. : 1950) Journal of Immunology, vol. 192, no. 1, pp. 200-205 |
| Popis: | Generating a diverse T cell memory population through vaccination is a promising strategy to overcome pathogen epitope variability and tolerance to tumor Ags. The effector and memory pool becomes broad in TCR diversity by recruiting high- and low-affinity T cells. We wanted to determine which factors dictate whether a memory T cell pool has a broad versus focused repertoire. We find that inflammation increases the magnitude of low- and high-affinity T cell responses equally well, arguing against a synergistic effect of TCR and inflammatory signals on T cell expansion. We dissect the differential effects of TCR signal strength and inflammation and demonstrate that they control effector T cell survival in a bim-dependent manner. Importantly, bim-dependent cell death is overcome with a high Ag dose in the context of an inflammatory environment. Our data define the framework for the generation of a broad T cell memory pool to inform future vaccine design. |
| Databáze: | OpenAIRE |
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