Abstract
Although B7 on APCs has a well-recognized role in T cell costimulation, little is known about the functional significance of constitutive and activation-induced B7 expression that also occurs on T cells. To analyze the role of B7 on T cells, B7-1/B7-2-deficient mice (B7 double knockout) and mice overexpressing B7-2 exclusively on T cells (B7-2 transgenic) were used as T cell donors for allogeneic transplant recipients, and graft-vs-host disease (GVHD) was assessed. B7 double-knockout T cells resulted in significant GVHD acceleration compared with wild-type T cells. Conversely, B7-2 transgenic donor T cells mediated reduced GVHD mortality compared with wild-type T cells. Data indicated that B7 expression on T cells down-regulated alloresponses through CTLA-4 ligation. This study is the first to provide definitive in vivo data illustrating the importance of T cell-associated B7 as a negative regulator of immune responses in a clinically relevant murine model of GVHD. The up-regulation of B7 on T cells may be an important component of normal immune homeostasis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Differentiation / immunology*
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Antigens, Differentiation / metabolism*
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Antigens, Differentiation / physiology
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B7-1 Antigen / biosynthesis*
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B7-1 Antigen / genetics
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B7-1 Antigen / metabolism
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B7-1 Antigen / physiology
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B7-2 Antigen
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Bone Marrow Transplantation / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CTLA-4 Antigen
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Cell Communication / genetics
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Cell Communication / immunology*
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Down-Regulation / genetics
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Down-Regulation / immunology*
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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 / mortality
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Graft vs Host Disease / prevention & control
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Ligands
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Lymphocyte Activation / genetics
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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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, Transgenic
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Receptors, Interleukin-2 / biosynthesis
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Up-Regulation / genetics
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Up-Regulation / immunology
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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CTLA-4 Antigen
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Cd86 protein, mouse
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Ctla4 protein, mouse
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Ligands
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Membrane Glycoproteins
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Receptors, Interleukin-2