Regulation of lymphoid homeostasis by IL-2 receptor signals in vivo
Regulation of lymphoid homeostasis by IL-2 receptor signals in vivo
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DOI：
10.4049/jimmunol.164.7.3527
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Willerford, DM
中科院分区：
文献类型：
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作者：
Leung, DTM;Morefield, S;Willerford, DM
高亲和力的IL-2R信号是体内外周淋巴细胞稳态所必需的。我们发现，在携带DO11.10 MHC ii类限制性TCR转基因或Ia β -null突变的小鼠中，CD25是调节外周T细胞所必需的，这表明MHC I类和ii类依赖性T细胞亚群是由IL-2R信号独立调节的。相反，CD25（-/-）小鼠血清IgG1水平的失调依赖于CD4(+) T细胞。T细胞在DO11.10 CD25（-/-）小鼠中的扩增并不优先于逃避TCR转基因排除等位基因的细胞，而是被rag2 -null突变抑制。总之，这些发现表明内源性TCR是触发T细胞扩增所必需的，但CD25调节由低特异性信号激活的T细胞。在转移到BALB/c小鼠正常淋巴室的CD25(-/-) T细胞中，DO11.10 T细胞响应同源银的扩增适度减少。此外，在缺乏CD25的情况下，激活诱导的克隆性收缩和细胞凋亡在体内是完整的。这些数据表明，高亲和力IL-2R信号的调节作用超出了对ag特异性反应的控制，并提示这些信号在控制旁观者T细胞活化方面发挥作用。
High-affinity IL-2R signals are required for peripheral lpmphoid homeostasis in vivo. We found that CD25 was required for regulation of peripheral T cells in mice bearing either the DO11.10 MHC class II-restricted TCR transgene or an Ia beta-null mutation, suggesting that MHC class I- and class II-dependent T cell subsets are regulated independently by IL-2R signals. In contrast, deregulation of serum IgG1 levels in CD25(-/-) mice was dependent on CD4(+) T cells. T cell expansion in DO11.10 CD25(-/-) mice was not preferential for cells escaping allelic exclusion by the TCR transgene, but was suppressed by a Rag-2-null mutation. Together, these findings suggest that endogenous TCR are required to trigger T cell expansion, but that CD25 regulates T cells activated by low-specificity signals. Expansion of DO11.10 T cells in response to cognate Ag was modestly reduced in CD25(-/-) T cells transferred into the normal lymphoid compartments of BALB/c mice. Moreover, activation-induced clonal contraction and apoptosis in vivo were intact in the absence of CD25, These data indicate that the regulatory role of high-affinity IL-2R signals extends beyond the control of Ag-specific responses and suggest a role for these signals in control of bystander T cell activation.