CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rβ-deficient mice:: implications for the nonredundant function of IL-2
CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rβ-deficient mice:: implications for the nonredundant function of IL-2
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DOI：
10.1016/s1074-7613(02)00367-9
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发表时间：
2002-08-01
期刊：
影响因子：
32.4
通讯作者：
Kong, L
中科院分区：
文献类型：
--
作者：
Malek, TR;Yu, AX;Kong, L
在IL-2 R β（-/-）小鼠（Tg -/-小鼠）中胸腺转基因表达野生型IL-2 R β后，与IL-2 R β缺陷小鼠相关的致死性自身免疫被预防。在此，我们发现在IL-2 R β（-/-）小鼠中不容易检测到CD 4（+）CD 25（+）调节性T细胞，但在Tg -/-小鼠中重建了功能性CD 4（+）CD 25（+）T细胞的产生。将正常的CD 4（+）CD 25（+）T细胞连续转移到新生的IL-2 R β缺陷小鼠中可以预防这种致命的自身免疫综合征。在无疾病的成年IL-2 R β缺陷受体小鼠中，CD 4（+）CD 25（+）T细胞以接近正常的频率存在，仅来源于供体，并依赖于IL-2进行扩增。这些观察结果表明，IL-2/IL-2 R系统的基本功能主要在于CD 4（+）CD 25（+）调节性T细胞的产生水平。
Lethal autoimmunity associated with IL-2Rbeta-deficient mice is prevented after thymic transgenic expression of wild-type IL-2Rbeta in IL-2Rbeta(-/-) mice (Tg -/- mice). Here, we show that CD4(+)CD25(+) regulatory T cells were not readily detected in IL-2Rbeta(-/-) mice, but the production of functional CD4(+)CD25(+) T cells was reconstituted in Tg -/- mice. Adoptive transfer of normal CD4(+) CD25(+) T cells into neonatal IL-2Rbeta-deficient mice prevented this lethal autoimmune syndrome. The CD4(+) CD25(+) T cells in disease-free adult IL-2Rbeta-deficient recipient mice were present at a near normal frequency, were solely donor-derived, and depended on IL-2 for expansion. These observations indicate that the essential function of the IL-2/IL-2R system primarily lies at the level of the production of CD4(+)CD25(+) regulatory T cells.