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When T cells are primed by dendritic cells (DCs) to initiate antigen-specific immune responses screening for matching antigen receptor-MHC/peptide pairs takes place in DC-T-cell conjugates. For an immune response DC-T-cell conjugates formed during priming events need to dissolve. Although detailed knowledge on molecules involved in the conjugate formation is available, dissolving of them has not been considered to be an active process. Here, we identify CYTIP (cytohesin-interacting protein) to mediate DC-T-cell deattachment. CYTIP, which is induced during maturation of DCs, shortly accumulates to the contact zones with T cells within the first hour of coculture. Specific silencing of CYTIP results in stronger adhesion of DCs to T cells and to fibronectin. When a need for deattachment is created in a T-cell priming assay by only partially loading DCs with antigen, CYTIP silencing causes reduced priming capacity. Thus, CYTIP allows DCs to actively control DC-T-cell interactions.

We report the induction and reduction of adenosine receptor A2a and A3 mRNAs, respectively, during maturation of human monocyte-derived dendritic cells. Adenosine, an immunomodulatory molecule, is unstable in vitro; therefore we tested a stable agonist, 5'-(N-ethylcarboxamido)-adenosine, to explore the effect of adenosine receptor activation on dendritic cell function. We clearly show that adenosine receptor engagement affects the migratory activity of dendritic cells in three distinct settings. In human skin explant culture experiments the emigration of epidermal and dermal dendritic cells was diminished by the addition of 5'-(N-ethylcarboxamido)-adenosine. In a murine contact hypersensitivity assay 5'-(N-ethylcarboxamido)-adenosine caused a reduction in the numbers of epidermal and dermal dendritic cells arriving in the draining lymph node. In a chemotaxis assay of human dendritic cells in response to macrophage inflammatory protein 3beta (MIP-3beta)/CCL19, adenosine caused a delay in transmigration. Expression of a number of molecules involved in dendritic cell migration (CCR5, MIP-3beta/CCL19, and MDR-1) was reduced. Importantly, all other features of dendritic cells tested--phenotype, antigen uptake, cytokine production, T cell activation, and the T cell subset induction--remained unchanged. Dendritic cells carry antigens from the periphery to secondary lymphoid organs, where initiation of immune responses occurs. Increased adenosine release may modulate immune responses by delaying the encounter of antigen-loaded dendritic cells with T cells.