A role for pref-1 and HES-1 in thymocyte development.
T lymphocyte development requires a series of interactions between developing thymocytes and thymic epithelial (TE) cells. In this paper we show that TE cells in the developing thymus express Pref-1, a Delta-like cell-surface molecule. In fetal thymus organ cultures (FTOC), thymocyte cellularity was increased by the exogenous dimeric Pref-1 fusion protein, but was reduced by the soluble Pref-1 monomer or anti-Pref-1 Ab. Dimeric Pref-1 in FTOC also increased thymocyte expression of the HES-1 transcription factor. Thymocyte cellularity was increased in FTOC repopulated with immature thymocytes overexpressing HES-1, whereas FTOC from HES-1-deficient mice were hypocellular and unresponsive to the Pref-1 dimer. We detected no effects of either Pref-1 or HES-1 on developmental choice among thymocyte lineages. These results indicate that Pref-1 expressed by TE cells and HES-1 expressed by thymocytes are critically involved in supporting thymocyte cellularity.
Kaneta
M
M
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
Osawa
M
M
Sudo
K
K
Nakauchi
H
H
Farr
A G
AG
Takahama
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005333:Fetus; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs / Q000276:immunology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000072056:Transcription Factor HES-1
D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C512925:Dlk1 protein, mouse; C489734:Hes1 protein, mouse