CD4+CD8- T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse
| Autor: | P J Blair, S J Bultman, J C Haas, B T Rouse, J E Wilkinson, V L Godfrey |
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| Rok vydání: | 1994 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 153:3764-3774 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.153.8.3764 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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