Induction of T Cell Development From Hematopoietic Progenitor Cells by delta-like-1 in Vitro

Immunity. 2002 Dec;17(6):749-56. doi: 10.1016/s1074-7613(02)00474-0.

Abstract

The molecular interactions provided by the thymic microenvironment that predicate T cell development remain obscure. Here, we show that a bone marrow stromal cell line ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic progenitors into CD4 CD8 double- and single-positive T cells. Both gammadelta-TCR(+) and alphabeta-TCR(+) T cells are generated, and CD8(+) TCR(hi) cells produce gamma-interferon following CD3/TCR stimulation. These results establish that expression of Delta-like-1 on stromal cells provides key signals for the induction of T cell lineage commitment, stage-specific progenitor expansion, TCR gene rearrangement, and T cell differentiation in the absence of a thymus. Thus, it is likely that Delta-like-1/Notch interactions by the thymus underpin its unique ability to promote lineage commitment and differentiation of T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cell Culture Techniques / methods
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Lineage / genetics*
  • Cell Lineage / immunology*
  • Gene Expression Regulation, Developmental / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Stromal Cells / cytology
  • Stromal Cells / immunology

Substances

  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • delta protein