Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory
- University College London, United Kingdom
- Columbia University, United States
- University of Glasgow, United Kingdom
- University of Oxford, United Kingdom
Abstract
Laboratory mice develop populations of circulating memory CD4+ T cells in the absence of overt infection. We have previously shown that these populations are replenished from naive precursors at high levels throughout life (Gossel et al., 2017). However, the nature, relative importance and timing of the forces generating these cells remain unclear. Here, we tracked the generation of memory CD4+ T cell subsets in mice housed in facilities differing in their 'dirtiness'. We found evidence for sequential naive to central memory to effector memory development, and confirmed that both memory subsets are heterogeneous in their rates of turnover. We also inferred that early exposure to self and environmental antigens establishes persistent memory populations at levels determined largely, though not exclusively, by the dirtiness of the environment. After the first few weeks of life, however, these populations are continuously supplemented by new memory cells at rates that are independent of environment.
Data availability
Following our invitation to make a revised submission, the code for mathematical models has been deposited on GitHub (https://github.com/marianowicka/memory-CD4-and-dirt.git) , and raw cell counts used for model fitting are provided as source data files, as featured in figures 1, 5 and 7.
Article and author information
Author details
Funding
National Institutes of Health (R01 AI093870)
- Thea Hogan
- Maria Nowicka
- Daniel Cownden
- Andrew J Yates
Medical Research Council (MR/P011225/1)
- Benedict Seddon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were performed according to the UCL Animal Welfare and Ethical Review Body and Home Office regulations under PPL 70-8310.
Copyright
© 2019, Hogan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory
eLife 8:e48901.
https://doi.org/10.7554/eLife.48901
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