Modulation of tryptophan catabolism by regulatory T cells
Modulation of tryptophan catabolism by regulatory T cells
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DOI：
10.1038/ni1003
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发表时间：
2003-12-01
影响因子：
30.5
通讯作者：
Puccetti, P
中科院分区：
文献类型：
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作者：
Fallarino, F;Grohmann, U;Puccetti, P
调节性T（T-R）细胞表现出细胞毒性T淋巴细胞相关抗原4（CTLA-4）的组成性表达，但CTLA-4在介导T-R细胞的调节功能中的功能尚不清楚。我们在这里显示，小鼠CD 4（+）CD 25（+）细胞，无论是静止或诱导过表达CTLA-4与CD 3的抗体处理，启动色氨酸catalysts在树突状细胞通过CTLA-4依赖性机制。这个过程需要树突状细胞表达B7和产生细胞因子。相反，在细菌脂多糖存在下培养的T-R细胞以CTLA-4非依赖性但依赖于色氨酸的方式诱导树突状细胞对色氨酸的催化。因此，免疫抑制性色氨酸催化剂在树突状细胞中的调节可能代表T-R细胞的主要作用机制。
Regulatory T (T-R) cells manifest constitutive expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T-R cells is unclear. We show here that mouse CD4(+)CD25(+) cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T-R cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan catabolism in dendritic cells might represent a major mechanism of action of T-R cells.