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The role of exogenous stimulation of CD40 by CD40 ligand (CD40L) in dendritic cell (DC) maturation, CC-chemokine production, and CCR5 receptor expression was examined using a soluble trimeric CD40L agonist protein (CD40LT). Stimulation of monocyte-derived DCs with CD40LT enhanced the production of the CC-chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES and diminished surface expression of CCR5. Based on these findings, the functional role of CD40LT stimulation on the ability of DCs to replicate and transmit HIV viral infection was studied. The addition of CD40LT to cocultures of naive CD4+ T cells and autologous DCs (T/DC) infected with the macrophage-tropic isolate, HIV BaL, caused a striking reduction in reverse transcriptase (RT) activity after 10 and 14 days of culture. The addition of a mixture of Abs against CC-chemokines abrogated the decrease in RT …