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Immature Dendritic Cells (DCs) Use Chemokines and Intercellular Adhesion Molecule (ICAM)-1, But Not DC-Specific ICAM-3-Grabbing Nonintegrin, to Stimulate CD4⁺ T Cells in the Absence of Exogenous Antigen¹

Eliana Real^*, Andrew Kaiser, Graça Raposo, Ali Amara, Alessandra Nardin, Alain Trautmann^* and Emmanuel Donnadieu^2,*

^* Département de Biologie Cellulaire, Institut Cochin, Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR)8104, IDM (Immuno-Designed Molecules), Institut Curie, CNRS UMR144, and Unité d’Immunologie Virale, Institut Pasteur, Paris, France

Dendritic cells (DCs) possess a number of unique features that distinguish them from other APCs. One such feature is their ability to trigger Ag-independent responses in T cells. Previous studies have focused on mature DCs, but the prevalence of this phenomenon in the resting-state immature DCs has never been considered. In this study, we show that, in the absence of Ag, human immature DCs trigger multiple responses in autologous primary CD4⁺ T cells, namely, increased motility, small Ca²⁺ transients, and up-regulation of CD69. These responses are particularly marked in CD4⁺ memory T cells. By using several experimental approaches, we found that DC-specific ICAM-3-grabbing nonintegrin plays no role in the induction of T cell responses, whereas ICAM-1/LFA-1 interactions are required. In addition, DC-produced chemokines contribute to the Ag-independent T cell stimulatory ability of DCs, because pertussis toxin-treated T cells exhibit diminished responses to immature DCs. More particularly, CCL17 and CCL22, which are constitutively produced by immature DCs, mediate both T cell polarization and attraction. Thus, immature DCs owe part of their outstanding Ag-independent T cell stimulatory ability to chemokines and ICAM-1, but not DC-specific ICAM-3-grabbing nonintegrin.

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