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PMID:7930593
| Citation |
Blair, PJ, Bultman, SJ, Haas, JC, Rouse, BT, Wilkinson, JE and Godfrey, VL (1994) CD4+CD8- T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 153:3764-74 |
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| Abstract |
Mice hemizygous for the X-linked mutation, scurfy (sf), exhibit a fatal lymphoreticular disease that is mediated by T lymphocytes. To evaluate the respective roles of CD4 or CD8 single positive T cells in scurfy disease, neonates were treated with mAbs directed against the CD4 or CD8 molecules. Whereas mice treated with an anti-CD8 Ab developed lesions and succumbed to disease at the same time (17 days) as their untreated scurfy littermates, mice treated with an anti-CD4 Ab lived up to 11 wk before developing scurfy disease. To insure a more complete elimination of the T cell subsets, the scurfy mutation was bred onto beta 2-microglobulin (beta 2m)-deficient (CD8-less) and CD4-deficient transgenic mouse lines. Whereas there was little moderation of disease in beta 2m-deficient scurfy mice, CD4-deficient scurfy mice had markedly decreased scurfy lesions and a prolonged life span, similar to that of anti-CD4-treated sf/Y mice. Additionally, scurfy disease was transplanted into H-2-compatible nude mice through the adoptive transfer of CD4+CD8- T cells, but not CD4-CD8+ T cells. Flow-cytometric analysis revealed that sf/Y mice have an increased percentage of activated CD4+ T cells in their lymph nodes. In addition, there is an increase in the in vitro production of cytokines in the cultured splenocytes of CD8-less, but not CD4-less, scurfy mice. These data suggest that CD4+ T cells are critical mediators of disease in the scurfy mouse. |
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| Keywords |
Animals; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology; Cytokines/metabolism; Immunity, Cellular; Immunologic Deficiency Syndromes/immunology; Immunophenotyping; Lymphocyte Depletion; Lymphoproliferative Disorders/genetics; Lymphoproliferative Disorders/immunology; Mice; Mice, Mutant Strains/immunology; Mice, Nude; T-Lymphocyte Subsets/immunology; beta 2-Microglobulin/deficiency |
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