Prethymic T-cell development defined by the expression of paired immunoglobulin-like receptors.
T cells are produced in the thymus from progenitors of extrathymic origin. As no specific markers are available, the developmental pathway of progenitors preceding thymic colonization remains unclear. Here we show that progenitors in murine fetal liver and blood, which are capable of giving rise to T cells, NK cells and dendritic cells, but not B cells, can be isolated by their surface expression of paired immunoglobulin-like receptors (PIR). PIR expression is maintained until the earliest intrathymic stage, then downregulated before the onset of CD25 expression. Unlike intrathymic progenitors, generation of prethymic PIR(+) progenitors does not require Hes1-mediated Notch signaling. These findings disclose a prethymic stage of T-cell development programmed for immigration of the thymus, which is genetically separable from intrathymic stages.
Masuda
Kyoko
K
Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Kubagawa
Hiromi
H
Ikawa
Tomokatsu
T
Chen
Ching-Cheng
CC
Kakugawa
Kiyokazu
K
Hattori
Masakazu
M
Kageyama
Ryoichiro
R
Cooper
Max D
MD
Minato
Nagahiro
N
Katsura
Yoshimoto
Y
Kawamoto
Hiroshi
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018398:Homeodomain Proteins / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse