Source:http://linkedlifedata.com/resource/pubmed/id/10477719
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1999-10-12
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pubmed:abstractText |
Expansion of early lymphoid progenitors requires interleukin-7 (IL-7), which functions through gamma(c)-mediated receptor activation of Jak3. Jak3 deficiency is a cause of severe combined immunodeficiency (SCID) in humans and mice. IL-3 activates many of the same signaling pathways as IL-7, such as Stat5, but achieves this effect through the activation of Jak2 rather than Jak3. We hypothesized that expansion of an IL-7-responsive precursor population through a Jak3-independent pathway using IL-3 may stimulate early lymphoid progenitors and restore lymphopoiesis in Jak3(-/-) mice. Newborn Jak3(-/-) mice that were injected with IL-3 demonstrated thymic enlargement, a 2- to 20-fold increase in thymocyte numbers, and up to a 10-fold expansion in the number of CD4(+), CD8(+), and B220(+)/IgM(+) splenic lymphocytes, consistent with an effect upon an early lymphoid progenitor population. In contrast to control mice, IL-3-treated Jak3(-/-) mice challenged with the allogeneic major histocompatibility complex (MHC) class I-bearing tumor P815 developed a specific CD8-dependent cytotoxic T lymphocyte (CTL) response. IL-3-treated mice also mounted influenza-specific CTL responses and survival was prolonged. The beneficial effects of IL-3 are proposed to be produced by stimulation of a lymphoid precursor population of IL-7Ralpha(+)/IL-3Ralpha(+) cells that we identified in wild-type bone marrow. In vitro, we show that an early IL-7R(+) lymphoid progenitor population expresses IL-3R and proliferates in response to IL-3 and that IL-3 activates Stat5 comparably to IL-7. Clinically, IL-3 may therefore be useful treatment for X-linked and Jak3-deficient SCID patients who lack bone marrow donors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Jak3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-7
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1906-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10477719-Animals,
pubmed-meshheading:10477719-Bone Marrow Cells,
pubmed-meshheading:10477719-Flow Cytometry,
pubmed-meshheading:10477719-Hematopoietic Stem Cells,
pubmed-meshheading:10477719-Interleukin-3,
pubmed-meshheading:10477719-Interleukin-7,
pubmed-meshheading:10477719-Janus Kinase 3,
pubmed-meshheading:10477719-Lymphocyte Activation,
pubmed-meshheading:10477719-Lymphocytes,
pubmed-meshheading:10477719-Mice,
pubmed-meshheading:10477719-Mice, Inbred BALB C,
pubmed-meshheading:10477719-Mice, Knockout,
pubmed-meshheading:10477719-Mice, SCID,
pubmed-meshheading:10477719-Protein-Tyrosine Kinases,
pubmed-meshheading:10477719-Receptors, Interleukin-7,
pubmed-meshheading:10477719-Signal Transduction
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pubmed:year |
1999
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pubmed:articleTitle |
Reconstitution of early lymphoid proliferation and immune function in Jak3-deficient mice by interleukin-3.
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pubmed:affiliation |
Howard Hughes Medical Institute, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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