Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination

by Veronika I. Zarnitsyna, Rama S. Akondy, Hasan Ahmed, Donald J. McGuire, Vladimir G. Zarnitsyn, Mia Moore, Philip L. F. Johnson, Rafi Ahmed, Kelvin W. Li, Marc K. Hellerstein, Rustom Antia 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 C D8 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 vaccinati on, whereas death rates continue to decline for much longer. Our results show that power laws can be predict...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research