Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA.
J Immunol. 2012 May 1;188(9):4376-84. doi: 10.4049/jimmunol.1101775. Epub 2012 Apr 2.
TCR signaling plays a critical role in regulatory T cell (Treg) development. However, the mechanism for tissue-specific induction of Tregs in the periphery remains unclear. We observed that surfactant protein A (SP-A)-deficient mice have impaired expression of Foxp3 and fewer CD25(+)Foxp3(+) Tregs after ex vivo stimulation and after stimulation with LPS in vivo. The addition of exogenous SP-A completely reversed this phenotype. Although SP-A is known to inhibit T cell proliferation under certain activation conditions, both IL-2 levels as well as active TGF-β levels increase on extended culture with exogenous SP-A, providing a key mechanism for the maintenance and induction of Tregs. In addition, kinetic suppression assays demonstrate that SP-A enhances the frequency of functional Foxp3(+) Tregs in responder T cell populations in a TGF-β-dependent manner. In mice treated with LPS in vivo, Tregs increased ∼160% in wild-type mice compared with only a 50% increase in LPS-treated SP-A(-/-) mice 8 d after exposure. Taken together, these findings support the hypothesis that SP-A affects T cell immune function by the induction of Tregs during activation.
T 细胞受体信号在调节性 T 细胞（Treg）发育中发挥着关键作用。然而，外周组织中 Treg 的特异性诱导机制仍不清楚。我们观察到，表面活性剂蛋白 A（SP-A）缺陷小鼠在体外刺激后和体内用 LPS 刺激后，Foxp3 的表达受损，CD25(+)Foxp3(+)Treg 减少。外源性 SP-A 的添加完全逆转了这种表型。尽管已知 SP-A 在某些激活条件下抑制 T 细胞增殖，但在延长培养中添加外源性 SP-A 会增加 IL-2 水平和活性 TGF-β 水平，为 Treg 的维持和诱导提供了关键机制。此外，动力学抑制试验表明，SP-A 以 TGF-β依赖性方式增强了应答性 T 细胞群体中功能性 Foxp3(+)Treg 的频率。在体内用 LPS 处理的小鼠中，与 LPS 处理的 SP-A(-/-)小鼠相比，野生型小鼠中的 Treg 增加了约 160%，而在暴露后 8 天仅增加了 50%。总之，这些发现支持了这样一种假设，即 SP-A 通过在激活过程中诱导 Treg 来影响 T 细胞免疫功能。
