TY - JOUR
T1 - Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early thymocyte development
AU - Banwell, CM
AU - Partington, Katharine
AU - Jenkinson, Eric
AU - Anderson, Graham
PY - 2000/1/1
Y1 - 2000/1/1
N2 - T cell precursor development depends upon poorly defined interactions between thymocyte precursors and stromal cells involving cell surface molecules, extracellular matrix (ECM) components and soluble growth factors. To determine whether presentation of soluble factors by ECM is involved in early T cell development, we analyzed expression of ECM components in individual thymic stromal subsets and investigated their ability to present ECM-associated IL-7, a factor known to be important during early thymocyte development. We show that MHC class II(+) thymic epithelium and fibroblasts - essential requirements for development of CD4(-)8(-)precursors - both show surface expression of ECM components such as fibronectin and heparan sulfate. Use of biotinylated IL-7 protein indicates that both cell types bind IL-7, while enzymatic disruption of specific ECM components indicates that IL-7 presentation by both cell types is dependent upon heparan sulfate. However, disruption of IL-7 presentation specifically on fibroblasts does not affect their ability to contribute to T cell development. Collectively, these data suggest that while ECM-mediated presentation of IL-7 may be a general function of thymic stromal cells during thymocyte development, heparan sulfate-mediated IL-7 presentation specifically by fibroblasts is not essential and that the specific requirement for fibroblasts in early development involves additional undefined interactions.
AB - T cell precursor development depends upon poorly defined interactions between thymocyte precursors and stromal cells involving cell surface molecules, extracellular matrix (ECM) components and soluble growth factors. To determine whether presentation of soluble factors by ECM is involved in early T cell development, we analyzed expression of ECM components in individual thymic stromal subsets and investigated their ability to present ECM-associated IL-7, a factor known to be important during early thymocyte development. We show that MHC class II(+) thymic epithelium and fibroblasts - essential requirements for development of CD4(-)8(-)precursors - both show surface expression of ECM components such as fibronectin and heparan sulfate. Use of biotinylated IL-7 protein indicates that both cell types bind IL-7, while enzymatic disruption of specific ECM components indicates that IL-7 presentation by both cell types is dependent upon heparan sulfate. However, disruption of IL-7 presentation specifically on fibroblasts does not affect their ability to contribute to T cell development. Collectively, these data suggest that while ECM-mediated presentation of IL-7 may be a general function of thymic stromal cells during thymocyte development, heparan sulfate-mediated IL-7 presentation specifically by fibroblasts is not essential and that the specific requirement for fibroblasts in early development involves additional undefined interactions.
UR - http://www.scopus.com/inward/record.url?scp=0033846546&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(2000)30:8<2125::AID-IMMU2125>3.0.CO;2-H
DO - 10.1002/1521-4141(2000)30:8<2125::AID-IMMU2125>3.0.CO;2-H
M3 - Article
C2 - 10940902
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
VL - 30
SP - 2125
EP - 2129
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -