Intravital imaging of recently activated naive T cells by Bohineust et al. has revealed that following a period of reduced motility and dendritic cell (DC) interaction lasting 3 to 30 hours, T cells dissociate from DCs and divide as motile, unassociated cells. Intrinsic changes in store-operated calcium entry in the newly activated T cells prevented further motility arrest by DCs. Forced TCR signaling in newly activated cells blocked mitosis, suggesting that the early phase of newly stimulated cells disfavors additional TCR signaling and favors clonal expansion.
T cells are primed in secondary lymphoid organs by establishing stable interactions with antigen-presenting cells (APCs). However, the cellular mechanisms underlying the termination of T cell priming and the initiation of clonal expansion remain largely unknown. Using intravital imaging, we observed that T cells typically divide without being associated to APCs. Supporting these findings, we demonstrate that recently activated T cells have an intrinsic defect in establishing stable contacts with APCs, a feature that was reflected by a blunted capacity to stop upon T cell receptor (TCR) engagement. T cell unresponsiveness was caused, in part, by a general block in extracellular calcium entry. Forcing TCR signals in activated T cells antagonized cell division, suggesting that T cell hyporesponsiveness acts as a safeguard mechanism against signals detrimental to mitosis. We propose that transient unresponsiveness represents an essential phase of T cell priming that promotes T cell disengagement from APCs and favors effective clonal expansion.
Author Info: (1) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France. Institut National de la Sante et de la Recherche Medicale, U1223,
Author Info: (1) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France. Institut National de la Sante et de la Recherche Medicale, U1223, Paris, France. (2) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France. Institut National de la Sante et de la Recherche Medicale, U1223, Paris, France. (3) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France. Institut National de la Sante et de la Recherche Medicale, U1223, Paris, France. (4) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France. Institut National de la Sante et de la Recherche Medicale, U1223, Paris, France. (5) Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, Paris, France philippe.bousso@pasteur.fr. Institut National de la Sante et de la Recherche Medicale, U1223, Paris, France.
