Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Human CD14hi monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression

Abstract

CD40L on CD4(+)T cells plays a vital role in the activation of antigen presenting cells (APC), thus catalyzing a positive feedback loop for T cell activation. Despite the pivotal juxtaposition of CD40L between APC and T cell activation, only a TCR stimulus is thought to be required for early CD40L surface expression. We show for the first time that CD40L expression on peripheral blood CD4(+)T cells is highly dependent upon a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3 and to a lesser extent CD80/86 contribute to this enhancement of CD40L expression, but are not themselves sufficient. The contact mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells (DC) also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid DC, B cell lymphoma lines, resting, activated, and EBV immortalized primary B cells all lack the capacity to up regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with APC activation while the late phase is related to B cell activation.