Abstract
Presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-TCR (H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV) on a nonselecting MHC background (H-2d or TAP-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive selection of functional CD4- CD8+ cells whose kinetics and efficiency were enhanced by nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive selection; however, together with nonselecting stroma and nominal peptide, there was inefficient positive. These results suggest multiple signaling in positive selection with selection events able to occur on multiple-cell types. The ease with which this model can be manipulated should greatly facilitate the resolution of the mechanisms of positive selection in normal and pathological states.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / analysis
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Antigens, Differentiation, T-Lymphocyte / analysis
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation
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Cells, Cultured
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Coculture Techniques
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H-2 Antigens / immunology
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Hematopoietic Stem Cells / physiology
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Lectins, C-Type
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Lymphocyte Activation
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Lymphocytic choriomeningitis virus / immunology
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Mice
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Mice, Transgenic
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Models, Immunological
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Peptides / immunology
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Signal Transduction
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Stromal Cells / immunology*
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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Thymus Gland / cytology*
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Thymus Gland / growth & development
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Thymus Gland / immunology
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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H-2 Antigens
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Lectins, C-Type
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Peptides
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Receptors, Antigen, T-Cell, alpha-beta