Abstract
Nackt mice, which are deficient in cathepsin-L (CTSL), show an early impairment during positive selection in the context of class II MHC molecules and as a consequence, the percentage and absolute number of CD4(+) thymocytes are significantly decreased. In this study, we show that lymph nodes from nackt mice are hypertrophied, showing normal absolute numbers of CD4(+) T cells and marked increases in the number of CD8(+) T lymphocytes. Basal proliferative levels are increased in the CD4(+) but not in the CD8(+) population. Lymph node T cells show increases in the expression of alpha(5), alpha(6), and beta(1) integrin chains. These alterations correlate with increases in the expression of extracellular matrix (ECM) components in lymph nodes. Interestingly, laminin, fibronectin, and collagen I and IV are markedly decreased in nackt thymus which shows an augmented output of CD8(+) cells. These results demonstrate that a mutation in the Ctsl gene influences the levels of ECM components in lymphoid organs, the thymic output, and the number of T cells in the periphery. They further raise the possibility that, by regulating the level of expression of ECM components in lymphoid organs, CTSL is able to broadly affect the immune system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / metabolism
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Cathepsin L
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Cathepsins / deficiency
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Cathepsins / genetics
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Cathepsins / physiology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Cell Proliferation
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Cysteine Endopeptidases / deficiency
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / physiology*
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Down-Regulation / genetics
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Extracellular Matrix Proteins / antagonists & inhibitors
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Extracellular Matrix Proteins / biosynthesis*
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Glycoproteins / biosynthesis
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Integrin alpha5 / biosynthesis
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Integrin alpha6 / biosynthesis
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Integrin beta1 / biosynthesis
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymphocyte Count
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology*
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Lymphoid Tissue / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Mutant Strains
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / metabolism*
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Thymus Gland / cytology*
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Thymus Gland / immunology*
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Thymus Gland / metabolism
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Up-Regulation / genetics
Substances
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Extracellular Matrix Proteins
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Glycoproteins
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Integrin alpha5
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Integrin alpha6
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Integrin beta1
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Cathepsins
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Cysteine Endopeptidases
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Cathepsin L
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Ctsl protein, mouse