Soluble CD14 acts as a negative regulator of human T cell activation and function

T cell activation is controlled by the coordination of stimulatory and negative regulatory signals which are not completely defined. In this study we tested for a possible direct effect of CD14 on the regulation of T cell activation and function. We show that soluble CD14 (sCD14) induces inhibition of antigen‐mediated peripheral blood mononuclear cells (PBMC) proliferation and anti‐CD3‐mediated proliferation of CD4+CD8−, CD4−CD8+ and CD4+CD8+ T cell clones. This effect is not due to cell death, but results from a marked inhibition of IL‐2 production. Proliferation of T cell clones due to exogenous IL‐2 is not affected by sCD14. We also found that sCD14 inhibits production of another Th1‐like cytokine, IFN‐γ and a Th2‐like cytokine, IL‐4. Importantly, sCD14 induces a progressive accumulation of the inhibitory protein IκB‐α. We show that sCD14 binds to activated T cells. Following cell activation, biotinylated sCD14 stains CD3+ PBMC, as well as human T cell clones with varying intensity. The binding is saturable, can be inhibited by excess of unlabeled sCD14 and, following binding, sCD14 is internalized. Collectively, these findings reveal a previously unrecognized function of sCD14, namely its capacity to negatively regulate T lymphocyte activation and function by interacting directly with activated T cells.