Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules.

摘要: The capacity of purified fibronectin to costimulate human T cell DNA synthesis was examined. Low concentrations immobilized fibronectin, but not soluble augmented anti-CD3-induced proliferation highly cells. In the absence anti-CD3 stimulation, did induce alone or in presence IL-2 phorbol dibutyrate. Although is present high serum, able when cells were cultured serum-containing medium. Immobilized collagen type I enhance stimulated responses, whereas gelatin (denatured collagen) and laminin responses modestly. effects gelatin, however, appeared be indirect, because it could medium devoid fibronectin. enhanced induced both CD45RA dim bright subsets within CD4+ CD8+ subpopulations cells, although with phenotype costimulated by lower Enhancement completely inhibited a mAb CD29, integrin beta 1-chain (4B4) variety other mAb. contrast its on proliferation, 4B4 only partially blocked binding fibronectin-coated macrowells. These findings suggested that interaction between receptor transduced signal merely stabilize CD3 complex. Further experiments confirmed this observation. Thus separate surface. augmentation also either VLA-4 VLA-5 combination two directly responses. Thus, at least receptors are involved fibronectin-mediated costimulation proliferation. studies indicate signals through receptors, VLA-5, augment therefore implicate extracellular matrix protein as an important influence regulating responsiveness vivo.