Abstract
Mice deficient for the expression of CTLA-4 develop a lethal lymphoproliferative syndrome and multiorgan inflammation leading to death at about 4 wk of age. Here we show that RAG2-deficient mice reconstituted with CTLA-4-deficient bone marrow do not develop a lymphoproliferative syndrome despite lymphocyte infiltration mainly into pericardium and liver. Moreover, RAG2-deficient mice reconstituted with a mixture of normal and CTLA-4-deficient bone marrow remain healthy and do not develop any disease. Thus, the lethal disease observed in CTLA-4-deficient mice is not T cell autonomous and can be prevented by factors produced by normal T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Abatacept
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Animals
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Antigens, CD
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics*
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Antigens, Differentiation / immunology*
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Bone Marrow Cells / immunology
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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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CD4-Positive T-Lymphocytes / pathology
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CTLA-4 Antigen
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Cell Movement / immunology
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Immunoconjugates*
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Liver / immunology
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Liver / pathology
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Lymphocyte Activation / genetics
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Lymphoproliferative Disorders / genetics*
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Lymphoproliferative Disorders / immunology*
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Lymphoproliferative Disorders / pathology
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Mice
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Mice, Congenic
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Mice, Inbred C57BL
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Mice, Knockout
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Pericardium / immunology
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Pericardium / pathology
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Radiation Chimera / genetics
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Radiation Chimera / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
Substances
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Antigens, CD
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Antigens, Differentiation
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CTLA-4 Antigen
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Ctla4 protein, mouse
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Immunoconjugates
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Abatacept