Fibronectin is a TH1-specific molecule in human subjects

Background : T[Subscript H]1 cell–mediated immunity is essential for host defense against a variety of intracellular pathogens, such as mycobacteria, salmonella, and Leishmania species. A major T[subscript H]1-mediated effector mechanism involves the IFN-γ–induced killing of the pathogen by infected macrophages. Objectives : The range of known T[subscript H]1-specific effector molecules is limited, especially in human subjects. We sought to identify novel effector molecules that might be involved in T[subscript H]1-mediated pathogen clearance. Methods : We performed microarray-based analysis of human T[subscript H]1 and T[subscript H]2 cells to identify T[subscript H]1-specific molecules. These analyses identified the extracellular matrix molecule fibronectin as a highly expressed T[subscript H]1-specific molecule. We examined the expression of fibronectin in a variety of human cell types by using real-time RT-PCR, ELISA, and Western blotting. We also studied the role of fibronectin in modulating monocyte phenotype using in vitro culture. Results : We show that human T[subscript H]1 cells constitutively express and secrete fibronectin after in vitro differentiation from naive precursors. Furthermore, we demonstrate that ex vivo human T[subscript H]1 cells selectively express fibronectin when compared with T[subscript H]2 cells. The predominant isoform of fibronectin expressed by T[subscript H]1 cells contains additional domains of the protein responsible for α4β1 integrin binding and activation of Toll-like receptor 4. We show that treatment of monocytes with T[subscript H]1 cell–derived fibronectin induces expression of the proinflammatory cytokine IL-6 while inhibiting IL-10 expression. Conclusions : Because fibronectin also plays a major role in the attachment and opsonization of numerous intracellular pathogens, we propose that it might be a critical molecule produced by T[subscript H]1 cells involved in pathogen eradication.