Abstract
Store-operated Ca(2+) entry (SOCE) is believed to be of pivotal importance in T cell physiology. To test this hypothesis, we generated mice constitutively lacking the SOCE-regulating Ca(2+) sensor stromal interaction molecule 1 (STIM1). In vitro analyses showed that SOCE and Ag receptor complex-triggered Ca(2+) flux into STIM1-deficient T cells is virtually abolished. In vivo, STIM1-deficient mice developed a lymphoproliferative disease despite normal thymic T cell maturation and normal frequencies of CD4(+)Foxp3(+) regulatory T cells. Unexpectedly, STIM1-deficient bone marrow chimeric mice mounted humoral immune responses after vaccination and STIM1-deficient T cells were capable of inducing acute graft-versus-host disease following adoptive transfer into allogeneic hosts. These results demonstrate that STIM1-dependent SOCE is crucial for homeostatic T cell proliferation, but of much lesser importance for thymic T cell differentiation or T cell effector functions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport / genetics
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Biological Transport / immunology
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Calcium Channels / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Proliferation*
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Cells, Cultured
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Coculture Techniques
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Disease Models, Animal
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Female
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Graft vs Host Disease / genetics
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Graft vs Host Disease / immunology
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Graft vs Host Disease / metabolism
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Homeostasis / genetics
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Homeostasis / immunology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Mutant Strains
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Stromal Interaction Molecule 1
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / transplantation
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / metabolism
Substances
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Calcium Channels
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Membrane Glycoproteins
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Stim1 protein, mouse
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Stromal Interaction Molecule 1