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 antigen.
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.
Real
Eliana
E
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, Institut Pasteur, Paris, France.
Kaiser
Andrew
A
Raposo
Graça
G
Amara
Ali
A
Nardin
Alessandra
A
Trautmann
Alain
A
Donnadieu
Emmanuel
E
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D037181:Lectins, C-Type / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D018799:Intercellular Adhesion Molecule-1; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C106230:CCL17 protein, human; C515482:CCL22 protein, human