Enhanced T Cell Reconstitution by Hematopoietic Progenitors Expanded Ex-Vivo Using the Notch Ligand Delta1
| Autor: | Barbara Varnum-Finney, Irwin D. Bernstein, Paul J. Martin, Mari H. Dallas |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Myeloid
Recombinant Fusion Proteins T-Lymphocytes T cell Cellular differentiation Immunology Notch signaling pathway Biology Ligands Biochemistry Mice medicine Animals Transplantation Homologous Progenitor cell Transplantation Transplantation Chimera Receptors Notch Hematopoietic Stem Cell Transplantation Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Differentiation Recovery of Function Cell Biology Hematology Hematopoietic Stem Cells Antigens Differentiation Protein Structure Tertiary Cell biology Haematopoiesis medicine.anatomical_structure Immunoglobulin G Stem cell |
| Zdroj: | Blood. 108:67-67 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v108.11.67.67 |
| Popis: | Previously, we demonstrated that activation of Notch receptors by culture of murine lin−Sca-1+c-kit+ (LSK) hematopoietic progenitors with the Notch ligand Delta1ext−IgG, consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG, promoted early T cell differentiation and increased the number of progenitors capable of short-term lymphoid and myeloid reconstitution. Here we show accelerated thymic engraftment and T cell recovery after hematopoietic cell transplantation (HCT) in recipients of LSK cells cultured with Delta1ext−IgG compared to recipients of non-cultured LSK cells. Furthermore, data suggest that accelerated T cell recovery resulted from progenitor cells induced towards T cell differentiation. 103 LSK cells cultured with Delta1ext−IgG generated an 108-fold increase in total number of cells compared to cutlure with control IgG. Using limiting dilution analysis we estimated the number of progenitors with T cell potential in 103 LSK cells was 2.3; after culture with Delta1ext−IgG, the number in the 1011 expanded product was 1.9×109, representing a 5×108-fold increase. Lethally irradiated mice received 105 BM cells along with 103 LSK cells or 106 Delta1ext−IgG-cultured cells. At 3 and 5 wks after HCT, blood samples from recipients of Delta1ext−IgG-cultured cells contained 9- and 3-fold higher numbers of CD3+ cells compared to recipients of LSK cells (p |
| Databáze: | OpenAIRE |
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