A profound deficiency in thymic progenitor cells in mice lacking Jak3.
Humans and mice with genetic deficiencies that lead to loss of signaling through common gamma-chain (gammac)-containing cytokine receptors have severe defects in B and T lymphocytes. In humans, these deficiencies lead to a complete absence of T cells, whereas in mice, small thymuses give rise to normal numbers of peripheral T cells. We have examined the first wave of developing T cells in Jak3-/-, IL-7-/-, and IL-7Ralpha-/- fetal mice, and have found a near absence of thymic progenitor cells. This deficiency is highlighted by the complete inability of Jak3-/- progenitor cells to reconstitute T cell development in the presence of competing wild-type cells. These data clearly demonstrate a strong common basis for the T cell deficiencies in mice and humans lacking gammac/Jak3 signaling pathways.
Baird
A M
AM
Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA.
Lucas
J A
JA
Berg
L J
LJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D007272:Injections, Intralymphatic; D053616:Janus Kinase 3; D007700:Kinetics; D008231:Lymphopenia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology
D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3