Intraclonal competition limits the fate determination of regulatory T cells in the thymus.
Intraclonal competition limits the fate determination of regulatory T cells in the thymus.
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由于自身反应性T细胞的缺失是不完整的，胸腺需要自然的Foxp3+CD4+调节性T细胞(Treg)来防止自身免疫。然而，T细胞受体(TCR)特异性在胸腺Treg细胞发育中的作用仍存在争议。为了解决这个问题，我们创造了一个转基因株系，表达自然产生的Treg细胞来源的TCR。令人惊讶的是，只有当抗原特异的Treg细胞前体在正常胸腺中以低克隆率(1%)存在时，才会发生有效的胸腺Treg细胞发育。使用逆转录病毒载体和骨髓嵌合体，我们观察到另外两个Treg细胞来源的TCR的类似行为。这些数据表明，胸腺Treg细胞的发育是一个TCR指导过程，涉及一个小生境，该小生境可以比正向选择的小生境低得多的克隆频率饱和。
Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T (Treg) cells is required for preventing autoimmunity. However, the role of T cell receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell-derived TCR. Surprisingly, efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (<1%) within a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar behavior with two other Treg cell-derived TCRs. These data demonstrate that thymic Treg cell development is a TCR-instructive process involving a niche which can be saturable at much lower clonal frequencies than the niche for positive selection.
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影响因子：
32.4
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15.3
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