title: A human thymic epithelial cell culture system for the promotion of lymphopoiesis from hematopoietic stem cells.
abstract: OBJECTIVE
  A human thymic epithelial cell (TEC) line expressing human leukocyte antigen-ABC and human leukocyte antigen-DR was engineered to overexpress murine Delta-like 1 (TEC-Dl1) for the purpose of establishing a human culture system that supports T lymphopoiesis from hematopoietic progenitor cells (HPCs).
  
  
  METHODS
  Cord blood or bone marrow HPCs were co-cultured with either the parental TEC line expressing low levels of the Notch ligands, Delta-like 1 and Delta-like 4, or with TEC-Dl1 to determine if these cell lines support human lymphopoiesis.
  
  
  RESULTS
  In co-cultures with cord blood or bone marrow HPCs, TEC-Dl1 cells promote de novo generation of CD7(pos)CD1a(pos) T-lineage committed cells. Most CD7(pos)CD1a(hi) cells are CD4(pos)CD8(pos) double-positive (DP). We found that TEC-Dl1 cells are insufficient to generate mature CD3(hi) CD4(pos) or CD3(hi) CD8(pos) single-positive (SP) T cells from the CD4(pos)CD8(pos) DP T cells; however, we detected CD3(lo) cells within the DP and SP CD4 and CD8 populations. The CD3(lo) SP cells expressed lower levels of interleukin-2Rα and interleukin-7Rα compared to CD3(lo) DP cells. In contrast to the TEC-Dl1 line, the parental TEC-84 line expressing low levels of human Notch ligands permits HPC differentiation to the B-cell lineage.
  
  
  CONCLUSIONS
  We report for the first time a human TEC line that supports lymphopoiesis from cord blood and bone marrow HPC. The TEC cell lines described herein provide a novel human thymic stroma model to study the contribution of human leukocyte antigen molecules and Notch ligands to T-cell commitment and maturation and could be utilized to promote lymphopoiesis for immune cell therapy.
authors.affiliation: Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago, 2160 First Avenue, Maywood, IL 60153, USA.
authors.forename: Britte C
authors.initials: BC
authors.lastname: Beaudette-Zlatanova
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Knight
authors.forename: Shubin
authors.initials: S
authors.lastname: Zhang
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stiff
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
authors.forename: Phong T
authors.initials: PT
authors.lastname: Le
mesh_terms: D002135:Calcium-Binding Proteins; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004847:Epithelial Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D038041:Lymphopoiesis; D008565:Membrane Proteins / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein