| Immune dysregulation in TGF-beta 1-deficient mice. | |
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MedLine Citation:
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PMID: 8051399 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Approximately 2 wk after birth, mice having a TGF-beta 1 null mutation (TGF-beta 1(-/-)) exhibit a progressive wasting syndrome and death. Associated with this phenotype is a multifocal infiltration of lymphocytes and macrophages into target organs, especially the heart, lungs, and salivary glands. To explore the consequences of TGF-beta 1 deficiency on the immune system, lymphocyte phenotype and function were analyzed. Initially, lymphoid organ architecture seemed to be normal and, as symptoms developed, the thymus decreased in size, whereas lymph nodes were enlarged. Phenotypically, the TGF-beta 1(-/-) lymphoid cells seemed to be more differentiated in the thymus and activated in the lymph nodes, but remarkably unaffected in the spleen. Moreover, TGF-beta 1(-/-) spleen and lymph nodes displayed enhanced numbers of proliferating cells, as measured by proliferating cell nuclear Ag and/or cyclin-dependent kinase levels. Consistent with this hyperproliferative response, constitutive levels of IL-2 mRNA were elevated in the thymus and both IL-2 and IL-2R mRNA were increased in the lymph nodes. In contrast with the activation profile of TGF-beta 1(-/-) lymphoid cells in vivo, mitogen challenge of these cells in vitro revealed suppressed proliferation that was associated with a defect in inducible IL-2 mRNA expression and IL-2 secretion. Moreover, the addition of rIL-2 restored the deficient mitogen-induced proliferation. The mechanism leading to T cell anergy remains unclear; however, these data confirm the essential role for TGF-beta 1 in maintaining normal immune function. |
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Authors:
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M Christ; N L McCartney-Francis; A B Kulkarni; J M Ward; D E Mizel; C L Mackall; R E Gress; K L Hines; H Tian; S Karlsson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 153 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1994 Sep |
Date Detail:
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Created Date: 1994-09-06 Completed Date: 1994-09-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1936-46 Citation Subset: AIM; IM |
Affiliation:
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Cellular Immunology Section, Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence DNA Primers / chemistry Gene Expression Immunophenotyping Interleukin-2 / genetics, pharmacology Lymphocyte Activation* Lymphoid Tissue / cytology Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data RNA, Messenger / genetics Receptors, Interleukin-2 / genetics Transforming Growth Factor beta / physiology* |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Interleukin-2; 0/RNA, Messenger; 0/Receptors, Interleukin-2; 0/Transforming Growth Factor beta |
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