Kornbluth RS, Kee K, Richman DD; Univ. of California, San Diego, CA.
CD40L is rapidly expressed (5 min-2 h) on the membranes of certain CD4+ and CD8+ T cells upon activation of the T cell receptor. Macrophages express CD40 and are activated upon contact with a CD40L-expressing cell. To study this further, 293 cells stably transfected with a human CD40L construct or the control empty vector were prepared, added to monocyte-derived macrophages cultures, and supernatants were collected. By ELISA, CD40L-293 cells (but not control 293 cells) induced 2-6 ng/ml of MIP-1alpha, 4-10 ng/ml of MIP-1 beta, and 0.3-0.6 ng/ml of RANTES in 24 h. Chemokine release commenced 3 h after CD40L stimulation. On a per cell per day basis, the amounts of MIP-1 produced exceed that of any T cell yet described. These data support the reported finding that macrophages and not CD8+ T cells are the principal beta-chemokine-producing cells in lymph nodes from HIV-infected individuals (N. Tedla et al., Amer J Pathol 1996;148:1367-73). Significantly, supernatants from the CD40L-stimulated macrophages completely protected purified CD4+ T cells from infection by NSI HIV-1. Dendritic cells have also been reported to produce MIP-1alpha following CD40L stimulation. These data suggest that CD40L-expressing T cells directed against HIV antigens may play a protective role by rapidly stimulating macrophages to produce HIV-suppressive beta-chemokines.
Keywords: AEGIS, Chemokines, CC, HIV, CD40 Ligand, Macrophages, Macrophage Inflammatory Protein-1, HIV-1, RANTES, HIV Infections, Chemokines, Antigens, CD4, Monocytes, T-Lymphocytes, HIV Long Terminal Repeat, Anti-HIV Agents, Antigens, CD8, Human, genetics, AIDS
