Centre International de recherche en Infectiologie (CIRI), Lyon, France
Mathematical modeling of memory CD8 T cells generation
Understanding the process and molecular regulation of CD8 T cell differentiation towards short-term cytotoxic effector and long-term protective memory cells is an important goal of vaccine research. Ideally, using appropriate mathematical models describing this biological process (i.e. naïve CD8 T cells differentiation in memory cells) and biological measurements of parameters such as phenotype (subsets or differentiation stages) and cell numbers, one should be able to predict the outcome of a CD8 response in terms of number of memory cells that are being generated, but also in terms of functional properties or quality of these cells. Although a flurry of markers associated with subsets of effector or memory cells have been described, their association with a differentiation stage or a subset of memory cells often remains ambiguous. In terms of using mathematical models to predict the number of memory cells generated, one of the main hurdles has been the lack of phenotypic markers allowing the discrimination between memory and effector cells. Using a transcriptome approach and single cell phenotyping, we have found that CD44/Mki67/Bcl2 co-expression define 4 differentiation stages corresponding to naive, early effector, late effector and memory CD8 T cells. Using the numbers of cells at these different stages, our model allows long-term prediction of memory cell numbers from a few early measurements.
We have also exploited formal approaches based on mathematical models using population sizes and dynamics to test potential progeny links between different phenotype-based subsets of effector and memory cells. Results were confirmed using pseudo-time differentiation algorithms.
- Brinza et al. 2016 Immune signatures of protective spleen memory CD8 T cells. Sci Rep 6, 37651
- Crauste et al. 2017 Identification of nascent memory CD8 T cells and modeling of their ontogeny. Cell Syst 4, 306–317.e4
- Grau 2018 et al. Antigen-induced but not innate memory CD8 T cells express NKG2D and are recruited to the lung parenchyma upon viral infection. J Immunol 200, 3635–3646
Contact: Antonio Peixoto (email@example.com)
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