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CS-A therapy in MRL-lpr/lpr mice: amelioration of immunopathology despite autoantibody production.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1987 Jan 01; Vol. 138 (1), pp. 157-63. - Publication Year :
- 1987
-
Abstract
- MRL-lpr/lpr mice spontaneously develop massive T cell lymphadenopathy, autoantibodies, and immune-mediated pathology. These mice are thought to be models of various human autoimmune diseases, including systemic lupus, Sjogren's syndrome, and rheumatoid arthritis. We have used cyclosporin A (CS-A) treatment as a tool by which the mechanisms of immune-mediated pathology might be dissected. CS-A was used because of its known preferential inhibition of T cell function and the marked expansion in MRL-lpr/lpr mice of an unusual L3T4-, Lyt-2-, 6B2+ T cell population. CS-A prevented lymphadenopathy and expansion of L3T4-, Lyt-2-, 6B2+ T cells in the peripheral lymph nodes, and also in the thymus. The increased expression of the c-myb and T cell receptor beta-chain genes associated with these unusual cells was also corrected. The finding of increased numbers of L3T4-, Lyt-2-, 6B2+ thymocytes in untreated mice suggests abnormal intrathymic differentiation in lpr/lpr mice, a defect that was corrected by CS-A. Treated mice had a marked decrease in arthritis and glomerulonephritis and significantly prolonged survival. These beneficial effects of CS-A occurred despite a lack of reduction in antibodies reactive with DNA, circulating immune complexes, rheumatoid factor titers, or immunoglobulin concentrations. These results demonstrate that the B cell hyperactivity of MRL-lpr/lpr mice can proceed without the T cell proliferative disease.
- Subjects :
- Animals
Antibody Formation
Antigen-Antibody Complex metabolism
Autoantibodies immunology
Autoimmune Diseases pathology
B-Lymphocytes immunology
Gene Expression Regulation drug effects
Kidney Diseases drug therapy
Lymph Nodes pathology
Lymphatic Diseases drug therapy
Mice
Proto-Oncogene Proteins genetics
Spleen pathology
Synovitis drug therapy
T-Lymphocytes immunology
Thymus Gland pathology
Autoimmune Diseases drug therapy
Cyclosporins therapeutic use
Mice, Inbred Strains immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 138
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 3537128