MATURE DENDRITIC CELLS RESPOND TO SDF-1, BUT NOT TO SEVERAL BETA-CHEMOKINES

Immature dendritic cells (DCs) are highly motile, but after differenti ation they stop migration. Chemokines are chemotactic cytokines that d irect leukocyte trafficking, therefore we looked for the expression an d function of chemokine receptors in immature and mature DCs. As a mod el, we used the human DCs that develop from CD14(+) peripheral blood m onocytes cultured with GM-CSF and IL-4. After 6-7 days in culture, the se cells have the characteristics of immature DCs, but can be induced to mature further by inflammatory stimuli or by monocyte conditioned m edium (MCM). Immature DCs express mRNA for CXCR4, CCR3 and CCR5. The r eceptors are expressed on the cell surface, as assessed with monoclona l antibodies, and are functional (with the exception of CCR3) as asses sed by CA(++) mobilization in response to specific chemokines. Further differentiation and maturation of DC in MCM causes a downregulation o f expression and function of the beta-chemokine receptors, while CXCR4 still remains, and signals a calcium flux on mature DCs. We argue tha t the downregulation of beta-chemokine receptors during maturation hel ps to stop DC movement after T cells have been identified in lymphoid organs or at sites of delayed-type hypersensitivity.