Termination of T cell priming relies on a phase of unresponsiveness promoting disengagement from APCs and T cell division

Author:

Bohineust Armelle12,Garcia Zacarias12,Beuneu Hélène12,Lemaître Fabrice12,Bousso Philippe12ORCID

Affiliation:

1. Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, Paris, France

2. Institut National de la Santé et de la Recherche Medicale, U1223, Paris, France

Abstract

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.

Funder

Institut Pasteur

Institut National de la Santé et de la Recherche Medicale

European Research Council

Ligue Contre le Cancer

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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