Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion

Abstract : T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in ‘chase-and-escape’ dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.
Liste complète des métadonnées

https://hal.inria.fr/hal-01237852
Contributeur : Tommaso Lorenzi <>
Soumis le : jeudi 3 décembre 2015 - 18:28:45
Dernière modification le : vendredi 31 août 2018 - 09:06:03

Lien texte intégral

Identifiants

Citation

Tommaso Lorenzi, Rebecca H. Chisholm, Matteo Melensi, Alexander Lorz, Marcello Delitala. Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion. Immunology, Wiley, 2015, 146 (2), pp.271-280. 〈10.1111/imm.12500〉. 〈hal-01237852〉

Partager

Métriques

Consultations de la notice

284