Activation of the ancestral polarity regulator protein kinase C zeta at the immunological synapse drives polarization of Th cell secretory machinery toward APCs.
A key feature in T lymphocyte biology is that Th cells rapidly polarize their secretory machinery toward cognate APCs. The molecular mechanisms of these dynamic Th cell responses and their impact on APC biology remain to be elucidated. In this study, we demonstrate that protein kinase Czeta (PKCzeta) is rapidly activated at the immunological synapse (IS) in human Th cells interacting with cognate dendritic cells (DCs) and that a functional PKCzeta is required for the polarization of Th cell secretory machinery toward DCs. We also show that PKCzeta-dependent Th cell polarization allows dedicated delivery of IFN-gamma and CD40L at the IS and is required for the activation of cognate DCs to IL-12 production. PKCzeta synaptic activation is a low-threshold phenomenon and, in Th cells interacting with multiple DCs, selectively occurs at the IS formed with the DCs offering the strongest stimulus leading to dedicated Th cell polarization. Our results identify the PKCzeta signaling pathway as a key component of the Th cell polarization machinery and provide a molecular basis for T cell-dedicated activation of cognate DCs.
Bertrand
Florie
F
Institut National de la Santé et de la Recherche Médicale, Unité 563, Section Dynamique Moléculaire des Interactions Lymphocytaires, Centre de Physiopathologie de Toulouse Purpan, France.
Esquerré
Michael
M
Petit
Anne-Elisabeth
AE
Rodrigues
Magda
M
Duchez
Sophie
S
Delon
Jérôme
J
Valitutti
Salvatore
S
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D010766:Phosphorylation / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000099221:Protein Kinase C zeta
D023201:CD40 Ligand; D007371:Interferon-gamma; D007527:Isoenzymes; D011493:Protein Kinase C; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099221:Protein Kinase C zeta