Fibronectin Co-Stimulates via the α5β1 Receptor IL-2, IL-4 Production by Splenic, Granuloma Lymphocytes of Schistosoma mansoni Infected Mice

In murine Schistosomiasis mansoni, soluble worm egg antigens (SEA) induce L3T4⁺ T helper cell-mediated chronic granulomatous inflammations around parasite eggs. Within the fully developed granuloma lymphocytes, macrophages, and eosinophils, fibroblasts are embedded in extracellular matrix (ECM) composed of fibronectin, laminin, glycosaminoglycans and collagens. The present study examined in vitro the putative co-stimulatory role of fibronectin (FN) in acute and chronic infection splenic and granuloma lymphocyte responses. Plate-bound FN enhanced the anti-CD3 MoAb stimulated normal and acute or chronic infection splenic lymphoproliferation by 20–32%. The co-stimulatory effect was evident in SEA stimulated acute but not chronic infection spleen cells. Proliferation of stimulated granuloma lymphocytes could not be up-regulated by immobilized FN. Plate-bound FN significantly enhanced IL-2 and IL-4 production by SEA-stimulated acute, but not chronic, infection granuloma lymphocytes. However, FN had no influence on the high level of IL-2, IL-4 production of anti-CD3 MoAb stimulated acute or chronic infection splenic or granuloma lymphocytes. Because in the antigen-stimulated acute infection spleen or granuloma cultures the co-stimulatory effect by FN was abrogated by the tripeptide (RGD) arg-gly asp, and anti α₅β₁ antibody, enhancement is attributed to signalling via the α₅β₁ integrin receptor of lymphocytes.