Expression and function of the fractalkine receptor CX3CR1 by T lymphocyte subpopulations was evaluated in healthy individuals. In CD8(+) T lymphocytes, CX3CR1 was expressed by and functional in both CD45RO(-) and CD45RO(+) cells. In CD4(+) T lymphocytes, CX3CR1 was expressed mainly by CD45RO(+) cells, and almost exclusively by activated HLA-DR(+) T lymphocytes. This receptor was functional in CD45RO(+) cells, but not in CD45RO(-) cells. Expression of fractalkine was detected by in situ hybridization and immunohistochemistry in endothelial cells of normal lung and thymus. In hyperplastic lymph nodes, fractalkine was expressed by endothelial cells of high endothelial venules and of subcapsular vessels, by follicular dendritic cells (FDC) and by some follicle lymphocytes. Fractalkine mRNA was constitutively present in the HK FDC-like cell line, and it was induced in vitro in B lymphocytes stimulated by an anti-micro or by a CD40 mAb. These findings indicate that fractalkine may contribute to the recruitment of effector T helper lymphocytes, either in peripheral tissues or in lymphoid organs. In these tissues, fractalkine and its receptor may favor contact within follicles between activated T helper lymphocytes, activated B lymphocytes and FDC, thus contributing to the maturation of the B lymphocyte response.