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J Immunol ; 165(7): 4095-104, 2000 Oct 01.
Article in English | MEDLINE | ID: mdl-11034421

ABSTRACT

Lupus disease is marked by B lymphocyte hyperactivity and the production of Abs to dsDNA. The production of these anti-dsDNA Abs is T lymphocyte dependent. However, it is not clear how CD4+ T lymphocytes provide help for B lymphocytes to produce IgG anti-dsDNA Abs. One possible mechanism is suggested by studies showing that human patients with systemic lupus erythematosus and lupus mice have increased numbers of CD40 ligand (CD40L)+ T and B lymphocytes. The results described in this study reveal that young, clinically healthy lupus-prone New Zealand Black x New Zealand White F1 (BWF1) mice have naive CD4+ T cells with preformed CD40L. These cells contribute to a brisk response to immunization and to the production of anti-dsDNA Abs. In vitro experiments revealed that CD4+ T cells with preformed CD40L could, upon stimulation, provide antiapoptotic signals for B cells but could not induce proliferation or reduce activation threshold. These results suggest that the direct target cells for the effect of T cells with preformed CD40L in lupus may not be B lymphocytes.


Subject(s)
Antibodies, Antinuclear/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD40 Ligand/immunology , Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Aging/genetics , Aging/immunology , Animals , Antibodies, Antinuclear/blood , Antigens/administration & dosage , Antigens/immunology , B-Lymphocytes/cytology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD40 Ligand/biosynthesis , Cell Aggregation/immunology , Cell Differentiation/immunology , Cell Division/genetics , Cell Division/immunology , Cell Survival/immunology , Cells, Cultured , Coculture Techniques , Crosses, Genetic , Cytoplasm/immunology , Cytoplasm/metabolism , DNA/immunology , Immunization , Immunophenotyping , Kinetics , Lupus Erythematosus, Systemic/pathology , Lymphocyte Activation , Lymphocyte Cooperation/immunology , Lymphocyte Count , Mice , Mice, Inbred CBA , Mice, Inbred NZB , Spleen/cytology , Spleen/immunology , Spleen/metabolism , T-Lymphocyte Subsets/pathology , Up-Regulation/genetics , Up-Regulation/immunology
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