Active form of Notch members can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.
The in vitro induction of T lymphopoiesis needs the precise stereoscopic structure of thymus tissues as seen in fetal thymus organ culture. In this study, we demonstrated for the first time that the introduction of the intracellular region of Notch1 can induce T cells expressing TCR without any thymic environment. In the coculture on the monolayer of OP-9, which was originally known to support B cell specific development, hemopoietic progenitors developed into Thy-1(+)CD25(+) T lineage cells if the progenitor cells were infected with the retrovirus containing Notch1 intracellular domains. The Thy-1(+) cells progressed to a further developmental stage, CD4 and CD8 double-positive cells expressing TCR on the cell surface, if they were further cultured on OP-9 or in the thymus. However, T cell induction by intracellular Notch1 failed unless both OP-9 and IL-7 were present. It is notable that Notch2 and Notch3 showed an effect on T lymphopoiesis similar to that of Notch1. These results indicate that in vitro T lymphopoiesis is inducible by signaling via Notch family members in a lineage-specific manner but shares other stroma-derived factors including IL-7 with B lymphopoiesis.
Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Katsuto
K
Hozumi
Natsumi
N
Abe
Shigeru
S
Chiba
Hisamaru
H
Hirai
Sonoko
S
Habu
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007424:Intracellular Fluid / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis
D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D020033:Protein Isoforms; D051880:Receptors, Notch; D018800:Thy-1 Antigens; D019009:Proto-Oncogene Proteins c-kit