A DENDRITIC-CELL-DERIVED C-C CHEMOKINE THAT PREFERENTIALLY ATTRACTS NAIVE T-CELLS

Dendritic cells form a system of highly efficient antigen-presenting c ells. After capturing antigen in the periphery, they migate to lymphoi d organs where they present the antigen to T cells(1,2). Their seeming ly unique ability to interact with and sensitize naive T cells gives d endritic cells a central role in the initiation of immune responses an d allows them to be used in therapeutic strategies against cancer, vir al infection and other diseases. How they interact preferentially with naive rather than activated T lymphocytes is still poorly understood. Chemokines direct the transport of white blood cells in immune survei llance(3,4). Here we report the identification and characterization of a C-C chemokine (DC-CK1) that is specifically expressed by human dend ritic cells at high levels. Tissue distribution analysis demonstrates that dendritic cells present in germinal centres and T-cell areas of s econdary lymphoid organs express this chemokine. We show that DC-CK1, in contrast to RANTES, MIP-1 alpha, and interleukin-8, preferentially attracts naive T cells (CD45RA(+)). The specific expression of DC-CK1 by dendritic cells at the site of initiation of an immune response, co mbined with its chemotactic activity for naive T cells, suggests that DC-CK1 has an important rule in the induction of immune responses.