Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early thymocyte development.
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.
Department of Anatomy, Division of Immunity and Infection, MRC Centre for Immune Regulation, Medical School, University of Birmingham, Birmingham, GB.
C M
CM
Banwell
K M
KM
Partington
E J
EJ
Jenkinson
G
G
Anderson
D000818:Animals; D004848:Epithelium / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006497:Heparan Sulfate / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015851:Interleukin-7 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology
D016326:Extracellular Matrix Proteins; D006497:Heparan Sulfate; D000949:Histocompatibility Antigens Class II; D015851:Interleukin-7