Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity
Michael Saitakis,
Stéphanie Dogniaux,
Christel Goudot,
Nathalie Bufi,
Sophie Asnacios,
Mathieu Maurin,
Clotilde Randriamampita,
Atef Asnacios,
Claire Hivroz
Affiliations
Michael Saitakis
Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France
Stéphanie Dogniaux
Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France
Christel Goudot
Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France
Nathalie Bufi
Laboratoire Matières et systèmes complexes, Université Paris-Diderot and CNRS, UMR 7057, Sorbonne Paris Cité, Paris, France
Sophie Asnacios
Laboratoire Matières et systèmes complexes, Université Paris-Diderot and CNRS, UMR 7057, Sorbonne Paris Cité, Paris, France; Department of Physics, Sorbonne Universités, UPMC Université Paris, Paris, France
Mathieu Maurin
Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France
Clotilde Randriamampita
INSERM, U1016, Institut Cochin & UMR8104, CNRS & Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Atef Asnacios
Laboratoire Matières et systèmes complexes, Université Paris-Diderot and CNRS, UMR 7057, Sorbonne Paris Cité, Paris, France
T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4+ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly.
