T cell polarity at the immunological synapse is required for CD154-dependent IL-12 secretion by dendritic cells.
Ag-specific interaction between T lymphocytes and dendritic cells (DCs) leads to both T cell and DC activation. CD154 (CD40 ligand)/CD40 interactions have been shown to play a major, although not exclusive, role in this functional cross-talk. Interactions between T cells and DCs are structured by an immunological synapse (IS), characterized by polarization of the T cell microtubule cytoskeleton toward the interacting DCs. Yet the role T cell polarization may play in T cell-induced DC activation is mostly unknown. In this study, we address the role of T cell polarity in CD154-dependent activation of DCs in a human model, using two different tools to block T cell polarity (i.e., a microtubule depolymerizing drug and an inhibitor of atypical protein kinase C). We show that CD154 is recruited and concentrated at the IS formed between human primary T cells and autologous DCs and that this recruitment requires T cell polarity at the IS. Moreover, we show that T cell polarization at the IS controls T cell-dependent CD154-CD40 signaling in DCs as well as CD154-dependent IL-12 secretion by DCs. This study shows that T cell polarity at the IS plays a key role in CD154/CD40-dependent cross-talk between CD4(+) T cells and DCs.
Tourret
Marie
M
Institut Curie, Centre de Recherche, Pavillon Pasteur and Institut National de la Santé et de la Recherche Médicale, Unité 932, Immunité et Cancer, Paris, France.
Guégan
Sarah
S
Chemin
Karine
K
Dogniaux
Stéphanie
S
Miro
Francesc
F
Bohineust
Armelle
A
Hivroz
Claire
C
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D054992:Immunological Synapses; D018664:Interleukin-12 / Q000378:metabolism*
D023201:CD40 Ligand; D018664:Interleukin-12