Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination
| Autor: | Veronika I. Zarnitsyna, Rustom Antia, Hasan Ahmed, Marc K. Hellerstein, Rafi Ahmed, Philip L. F. Johnson, Donald J. McGuire, Vladimir G. Zarnitsyn, Kelvin W. Li, Rama Akondy, Mia Moore |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Composite Particles
Vaccine evaluation CD8-Positive T-Lymphocytes White Blood Cells Isotopes Animal Cells Medicine and Health Sciences Cytotoxic T cell Public and Occupational Health Cell Cycle and Cell Division Biology (General) Cell Analysis media_common Ecology Cell Death T Cells Mortality rate Physics Dynamics (mechanics) Yellow fever Yellow Fever Vaccine Longevity Vaccination and Immunization Vaccination medicine.anatomical_structure Bioassays and Physiological Analysis Computational Theory and Mathematics Cell Division Analysis Cell Processes Modeling and Simulation Physical Sciences Yellow fever virus Cellular Types medicine.drug Research Article Atoms Death Rates QH301-705.5 media_common.quotation_subject T cell Immune Cells Immunology Yellow fever vaccine Cytotoxic T cells Biology Research and Analysis Methods Cellular and Molecular Neuroscience Population Metrics Genetics medicine Humans Particle Physics Molecular Biology Ecology Evolution Behavior and Systematics Blood Cells Population Biology Models Immunological Computational Biology Biology and Life Sciences Cell Biology medicine.disease Deuterium Immunization Preventive Medicine Immunologic Memory |
| Zdroj: | PLoS Computational Biology, Vol 17, Iss 10, p e1009468 (2021) PLoS Computational Biology |
| ISSN: | 1553-7358 |
| Popis: | Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency of YFV-specific memory CD8 T cells and deuterium enrichment in those cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.1% per day, ∼ double the estimated values for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically. Author summary Immunological memory, generated in response to infection or vaccination, may provide complete or partial protection from antigenically similar infections for the lifetime. Memory CD8 T cells are important players in protection from secondary viral infections but quantitative understanding of their dynamics in humans is limited. We analyze data from two studies where immunization with the yellow fever virus vaccine (YFV-17D) generates a mild acute infection and long-term memory. We find that: (i) the division rate of YFV-17D-specific CD8 T cells drops and stabilizes at ∼ 0.1% per day during the first year following vaccination whereas the death rate declines more gradually, and (ii) the number of these cells declines approximately in accordance with a power law (∝ time−0.75) for at least several decades following vaccination. |
| Databáze: | OpenAIRE |
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