Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Immunology. 2010 Oct;131(2):289-99. doi: 10.1111/j.1365-2567.2010.03304.x.
Invariant natural killer T (iNKT) cells are known to constitutively express the high affinity interleukin-2 receptor α chain (CD25) in neonates, but the functional consequence of this phenotype is unknown. Here, we show that high numbers of CD25-expressing iNKT cells are present early in gestation and represent a significant proportion of the developing immune system. Despite their activated phenotype, neonatal iNKT cells express high levels of the Krüppel-like factor-2, a transcription factor associated with quiescent T cells, and require de novo T-cell receptor and CD28 co-stimulation to proliferate. In contrast to bona fide CD4/CD25-expressing regulatory T cells, neonatal iNKT cells do not suppress T-cell responses, indicating that they do not represent an immunosuppressive cell subset. Evidence that neonatal iNKT cells respond to dramatically reduced amounts of CD1d-restricted antigen compared with adult iNKT cells or T cells, and that their proliferation can be induced in the absence of early interleukin-2 suggest that constitutive expression of CD25 'primes' neonatal iNKT cells to respond rapidly to low amounts of antigen. This unique phenotype, which is distinct from adult iNKT cells, as well as other CD25-expressing activated T or regulatory T cells, may be important to ensure stability of a structurally limited peripheral iNKT-cell repertoire early in life.
天然不变自然杀伤 T(iNKT)细胞在新生儿中已知持续表达高亲和力白细胞介素-2 受体 α 链(CD25)，但其表型的功能后果尚不清楚。在这里，我们表明，大量表达 CD25 的 iNKT 细胞在妊娠早期存在，并代表了正在发育中的免疫系统的重要组成部分。尽管它们具有激活表型，但新生儿 iNKT 细胞表达高水平的 Krüppel 样因子-2，这是一种与静止 T 细胞相关的转录因子，并且需要新的 T 细胞受体和 CD28 共刺激来增殖。与真正的 CD4/CD25 表达调节性 T 细胞不同，新生儿 iNKT 细胞不抑制 T 细胞反应，表明它们不代表一种免疫抑制细胞亚群。有证据表明，与成年 iNKT 细胞或 T 细胞相比，新生儿 iNKT 细胞对明显减少的 CD1d 限制性抗原作出反应，并且它们的增殖可以在没有早期白细胞介素-2 的情况下诱导，这表明 CD25 的组成性表达“启动”新生儿 iNKT 细胞对低量抗原的快速反应。这种独特的表型与成年 iNKT 细胞以及其他表达 CD25 的激活 T 细胞或调节性 T 细胞不同，可能对于确保生命早期结构有限的外周 iNKT 细胞库的稳定性很重要。
