Studies on the role of IL-7 presentation by mesenchymal fibroblasts duringearly thymocyte development

T cell precursor development depends upon poorly defined interactions betwe en thymocyte precursors and stromal cells involving cell surface molecules, extracellular matrix (ECM) components and soluble growth factors. To deter mine whether presentation of soluble factors by ECM is involved in early T cell development, we analyzed expression of ECM components in individual th ymic stromal subsets and investigated their ability to present ECM-associat ed IL-7, a factor known to be important during early thymocyte development. We show that MHC class II' thymic epithelium and fibroblasts - essential r equirements for development of CD4(-)8(-)precursors - both show surface exp ression of ECM components such as fibronectin and heparan sulfate. Use of b iotinylated IL-7 protein indicates that both cell types bind IL-7, while en zymatic disruption of specific ECM components indicates that IL-7 presentat ion by both cell types is dependent upon heparan sulfate. However, disrupti on of IL-7 presentation specifically on fibroblasts does not affect their a bility to contribute to T cell development. Collectively, these data sugges t that while ECM-mediated presentation of IL-7 may be a general function of thymic stromal cells during thymocyte development, heparan sulfate-mediate d IL-7 presentation specifically by fibroblasts is not essential and that t he specific requirement for fibroblasts in early development involves addit ional undefined interactions.