Abstract
The effect of B7-mediated costimulation on T cell homeostasis was examined in studies of B7-1 (CD80) and B7-2 (CD86) transgenic as well as B7-deficient mice. B7 overexpression in transgenic mice resulted in marked polyclonal peripheral T cell hyperplasia accompanied by skewing toward an increased proportion of CD8 single-positive cells and a decreased proportion of CD4 single-positive cells in thymus and more markedly in peripheral T cells. B7-induced T cell expansion was dependent on both CD28 and TCR expression. Transgenic overexpression of B7-1 or B7-2 resulted in down-regulation of cell surface CD28 on thymocytes and peripheral T cells through a mechanism mediated by intercellular interaction. Mice deficient in B7-1 and B7-2 exhibited changes that were the reciprocal of those observed in B7-overexpressing transgenics: a marked increase in the CD4/CD8 ratio in peripheral T cells and an increase in cell surface CD28 in thymus and peripheral T cells. These reciprocal effects of genetically engineered increase or decrease in B7 expression indicate that B7 costimulation plays a physiological role in the regulation of CD4+ and CD8+ T cell homeostasis.
MeSH terms
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Abatacept
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Animals
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, CD / physiology*
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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B7-1 Antigen / biosynthesis
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B7-1 Antigen / genetics
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B7-1 Antigen / physiology*
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B7-2 Antigen
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CD28 Antigens / biosynthesis
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CD28 Antigens / genetics
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CD28 Antigens / physiology
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CD4-CD8 Ratio
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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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 / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CTLA-4 Antigen
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Down-Regulation / genetics
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Down-Regulation / immunology
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Homeostasis / genetics
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Homeostasis / immunology*
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Hyperplasia
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Immunoconjugates*
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Lymphocyte Activation / genetics
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Lymphoid Tissue / pathology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Congenic
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Mice, Transgenic
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Phenotype
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Receptors, Antigen, T-Cell / biosynthesis
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CTLA-4 Antigen
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Cd86 protein, mouse
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Ctla4 protein, mouse
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Immunoconjugates
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Abatacept