Abstract
The CD28 costimulatory receptor has a pivotal role in T cell biology as this molecule amplifies T cell receptor (TCR) signals to provide an efficient immune T cell response. There is a large debate about how CD28 mediates these signals. Here, we designed a CD28 gene-targeted knock-in mouse strain lacking the cytoplasmic tail of CD28. As is the case in CD28-deficient (CD28 knock-out) mice, regulatory T cell homeostasis and T cell activation are altered in these CD28 knock-in mice. Unexpectedly, the presence of a CD28 molecule deprived of its cytoplasmic tail could partially induce some early activation events in T cells such as signaling events or expression of early activation markers. These results unravel a new mechanism of T cell costimulation by CD28, independent of its cytoplasmic tail.
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Acknowledgments
We thank Valérie Ferrier-Depraetere (Institut Paoli-Calmettes) for thoughtful reading of the manuscript. We are grateful to Pr. Doreen A. Cantrell (University of Dundee) for sharing her expertise in the “animal models and T cell signaling” research field. We are indebted to Anne-Marie Mura and Mireille Richelme for their help to handle and manipulate mouse ES cells, to Danielle Depetris and Dr Marie-Geneviève Mattei for analyzing chromosome stability of ES cells, to Dr Cécile Goujet (SEAT, Villejuif) for injecting selected ES clones, to Nacer Boubenna for his help in the initial steps of the description of CD28 KI mouse strain, to Emilie Coppin (CRCM) and Marisa Goncalves Menoita (CIML) for their help in the biochemical assays and to Dr Anne-Marie Schmitt-Verhulst (CIML) for helpful discussions. The authors thank to Patrick Gibier, Jean-Christophe Orsoni (CRCM animal facility) and Fabrice Gianardi (inter-IFR animal facility) for taking care of the mouse strain colonies and the CRCM cytometry platform for FACS analysis. This work was supported by institutional grants from the Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique and Aix-Marseille Université to CRCM and the Comité du Var de la Ligue Nationale contre le Cancer (J.A.N.). J.A. Nunès and D. Olive laboratory is supported by the Fondation pour la Recherche Médicale (Equipe FRM DEQ 20140329534). V. Giroux was supported by a fellowship from the Fondation pour la Recherche Médicale, S.O. Morin by a fellowship from Aix-Marseille Université, C. Favre by fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche and the Association pour la Recherche contre le Cancer. D. Olive is a scholar of the Institut Universitaire de France.
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S. O. Morin , V. Giroux , and C. Favre contributed equally to this work.
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Morin, S.O., Giroux, V., Favre, C. et al. In the absence of its cytosolic domain, the CD28 molecule still contributes to T cell activation. Cell. Mol. Life Sci. 72, 2739–2748 (2015). https://doi.org/10.1007/s00018-015-1873-7
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DOI: https://doi.org/10.1007/s00018-015-1873-7