Rôle de l’Inflammation sur la Rhéologie des Cellules Présentatrices d’Antigène : Perspectives pour l’Activation du Lymphocyte T

Abstract : T Lymphocyte activation is a crucial event in immune responses, since it is the first and necessary step for the initiation of adaptative responses. During this activation process, the T lymphocyte forms a contact with myeloid antigen presenting cells, the only cells able to trigger the engagement of the T cell receptor. While myeloid antigen presenting cells have various shape and sizes, T cell activation requires cytoskeleton remodeling. Besides, it has been shown that T lymphocytes may exert forces on antigen presenting cells, and that T cell signaling can be triggered after purely mechanical sollicitation of the TCR : these are all clues for T cell mecanosensitivity during activation. We thus took advantage of the emerging field of cell biomechanics, for the understanding of these phenomena. We first measured the mechanical properties of antigen presenting cells, and their mo- dification upon inflammatory treatments. We discovered that the presenting cells rigidity span over a very wide range, and that it can be affected by inflammatory conditions. The evolution of rigidity upon inflammation was independent of the evolution of maturation molecules at the cell surface. We therefore identified rigidity as a new marker of inflammation. Following these results, we conducted experiments in order to decipher the underlying molecular mechanisms to these varying rigidities. We observed that while the composition of each cell type in cytoskeleton proteins is very variable, it re- mains stable throughout inflammatory treatments. This suggests that the differentiation in a myeloid type implies deep structural modifications, that are likely to be coupled to functional changes. Last, we developped a protocol for the fabrication of soft gels of controled rigidity. We then used these gels for T lymphocyte activation on substrates of varying rigidity, and the preliminary results of these experiments are presented. Overall, by providing the rigidity range to which T lymphocyte is exposed during the interaction with myeloid antigen presenting cells, this study establishes a solid basis for further investigation of T lymphocyte mecanosensitivity.
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Nathalie Bufi. Rôle de l’Inflammation sur la Rhéologie des Cellules Présentatrices d’Antigène : Perspectives pour l’Activation du Lymphocyte T. Biophysique [physics.bio-ph]. Université Paris Diderot, 2014. Français. ⟨tel-01131751⟩

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