CD40L at the interface of the innate and adaptive immune responses. (P5206)

Abstract

Abstract Induction of CD40L expression on CD4+ T cells is a critical event in the generation of cellular and humoral immune responses. CD40L interacts with B cells via its cognate receptor to trigger immunoglobulin isotype class switching and promote Ig secretion and the differentiation of memory B cells. Through its induction of IL-12 and upregulation of costimulatory molecules on antigen presenting cells (APC), CD40L is also vital to the generation of Th1 cellular responses. We have previously demonstrated that a combination of cell-contact dependent and soluble signals act in concert to orchestrate the biphasic pattern of CD40L expression that underlie its complex role in promoting the adaptive immune response. We now report that CD40L likely plays an equally important role in the innate response. We show for the first time that TCR-dependent expression of CD40L on primary human T cells can be induced by interaction of β1 integrins on CD4+ T cells with extracellular matrix (ECM) in a monocyte and IL-2 independent fashion. We provide evidence in a model of vascular wall injury that ECM mediated induction of CD40L on CD4+ T cells plays a role in wound healing. These findings establish a pivotal role for CD40L at the interface of the innate and adaptive immune responses and suggest that therapeutic modalities directed towards CD40L may have benefit in modulating vascular pathophysiology.