Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population
| Autor: | Stephen M. Hedrick, John T. Chang, Kyla D. Omilusik, Hongtuyet Nguyen, Matthew S. Tsai, Clara Toma, J. Justin Milner, Arnaud Delpoux, Miguel Reina-Campos, Ananda W. Goldrath, Brigid S. Boland |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cells 1.1 Normal biological development and functioning Population T cells Biology CD8-Positive T-Lymphocytes immunology Vaccine Related 03 medical and health sciences Mice 0302 clinical medicine Memory cell T-Lymphocyte Subsets memory T cells Underpinning research medicine Cytotoxic T cell Animals Humans 2.1 Biological and endogenous factors Mass cytometry Cell Lineage Aetiology education Transcription factor Cells Cultured education.field_of_study Multidisciplinary Cultured Effector Intracellular parasite Prevention Inflammatory and immune system Cell Differentiation Biological Sciences infection Cell biology 030104 developmental biology medicine.anatomical_structure Memory T cell Immunologic Memory 030215 immunology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 41 Proc Natl Acad Sci U S A |
| Popis: | Memory CD8 T cells provide durable protection against diverse intracellular pathogens and can be broadly segregated into distinct circulating and tissue-resident populations. Paradigmatic studies have demonstrated circulating memory cells can be further divided into effector memory (Tem) and central memory (Tcm) populations based on discrete functional characteristics. Following resolution of infection, we identified a persisting antigen-specific CD8 T cell population that was simultaneously terminally-fated with potent effector function but maintained memory T cell qualities and conferred robust protection against reinfection. Notably, this terminally-differentiated effector memory CD8 T cell population (terminal-Tem) was conflated within the conventional Tem population, prompting redefinition of the classical characteristics of Tem cells. Murine terminal-Tem were transcriptionally, functionally, and developmentally unique compared to Tem cells. Through mass cytometry and single-cell RNAseq analyses of human peripheral blood from healthy individuals, we also identified an analogous terminal-Tem population of CD8 T cells that was transcriptionally distinct from Tem and Tcm. A key finding of this study was that parsing of terminal-Tem from conventionally defined Tem challenges classical characteristics of Tem biology, including enhanced presence in lymphoid tissues, robust IL-2 production and recall potential, greater than expected homeostatic fitness, refined transcription factor dependencies, and a distinct molecular phenotype. Classification of terminal-Tem and clarification of Tem biology hold broad implications for understanding the molecular regulation of memory cell states and harnessing immunological memory to improve immunotherapies. |
| Databáze: | OpenAIRE |
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