Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Departamento de Medicina, Unidad de Internación 1, Hospital General de Niños "Pedro de Elizalde", Buenos Aires, Argentina.
J Infect Dis. 2018 Jun 5;218(1):75-83. doi: 10.1093/infdis/jiy180.
FOXP3+ regulatory T cells (Tregs) restrain the destructive potential of the immune system. We have previously reported a pronounced reduction in circulating Tregs in infants with severe respiratory syncytial virus (RSV) disease. Because interleukin-2 (IL-2) is critical for Treg growth, survival, and activity, we here analyzed IL-2 production and function in RSV-infected infants.
Phenotype, proliferation, IL-2 production, and IL-2 signaling in CD4+ T cells were analyzed by flow cytometry. Serum soluble CD25 levels were quantified by ELISA.
CD4+ T cells from RSV-infected infants produced lower amounts of IL-2 and showed a reduced proliferative response compared with healthy infants. IL-2 increased CD4+ T-cell proliferation and FOXP3 expression in both healthy and RSV-infected infants. However, although IL-2 induced a similar pattern of STAT5 phosphorylation, the proliferative response of CD4+ T cells and the expression of FOXP3+ remained significantly lower in RSV-infected infants. Interestingly, we found a negative correlation between disease severity and both the production of IL-2 by CD4+ T cells and the ability of exogenous IL-2 to restore the pool of FOXP3+CD4+ T cells.
A reduced ability to produce IL-2 and a limited response to this cytokine may affect the function of CD4+ T cells in RSV-infected infants.
FOXP3+调节性 T 细胞（Tregs）抑制免疫系统的破坏性潜能。我们之前报道过，严重呼吸道合胞病毒（RSV）疾病患儿的循环 Tregs 明显减少。由于白细胞介素-2（IL-2）对 Treg 的生长、存活和活性至关重要，因此我们在此分析了 RSV 感染婴儿的 IL-2 产生和功能。
通过流式细胞术分析 CD4+T 细胞的表型、增殖、IL-2 产生和 IL-2 信号转导。通过 ELISA 定量测定血清可溶性 CD25 水平。
与健康婴儿相比，RSV 感染婴儿的 CD4+T 细胞产生的 IL-2 量较少，增殖反应降低。IL-2 增加了健康婴儿和 RSV 感染婴儿的 CD4+T 细胞增殖和 FOXP3 表达。然而，尽管 IL-2 诱导了相似的 STAT5 磷酸化模式，但 RSV 感染婴儿的 CD4+T 细胞增殖反应和 FOXP3+表达仍然明显较低。有趣的是，我们发现 CD4+T 细胞产生的 IL-2 量和外源性 IL-2 恢复 FOXP3+CD4+T 细胞池的能力与疾病严重程度呈负相关。
产生 IL-2 的能力降低和对这种细胞因子的反应有限可能会影响 RSV 感染婴儿 CD4+T 细胞的功能。
