Betts Richard J, Kemeny D Michael
Immunology Program and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore.
Pharmacol Ther. 2009 Feb;121(2):123-31. doi: 10.1016/j.pharmthera.2008.09.001. Epub 2008 Oct 1.
While it is well established that CD4(+) T lymphocytes play a crucial role in the initiation, progression and persistence of asthma, the role of CD8(+) T cells is less understood. CD8(+) T cells form functionally similar subsets which exhibit similar cytokine profiles as Th1 and Th2 cells, known as Tc1 and Tc2. Evidence from animal studies suggest that CD8(+) T cells are capable of regulating IgE production through the induction of IL-12 and IL-18 production in dendritic cells, and that CD8(+) T cells may act to moderate Th2 polarisation within the localised lymph nodes during allergic sensitisation. Such findings have led to the suggestion that Th1 polarising, CD8(+) T cell-inducing vaccines would inhibit the development of airway hyperresponsiveness (AHR) and Th2 cell infiltration. Despite these positive findings, the role of CD8(+) T cells within the lung remains poorly understood. While CD8(+) T cells, particularly those expressing the Tc1 phenotype, are capable of moderating inflammation and suppressing AHR, it has been postulated that Tc2 CD8(+) T cells predominate within established asthma and may act to amplify the inappropriate immune response which defines the condition. Within the clinic, the association between CD8(+) T cells and asthma is almost universally defined as injurious, further suggesting a prejudicial role for these cells within the established disease. CD8(+) T cells may be a valuable potential target for therapeutic intervention, either by potentiating their regulatory effects prior to the development of sensitisation, or through suppressing their pro-inflammatory properties within established atopy.
虽然已经充分明确CD4(+) T淋巴细胞在哮喘的起始、进展和持续过程中起关键作用,但CD8(+) T细胞的作用却了解较少。CD8(+) T细胞形成功能相似的亚群,这些亚群表现出与Th1和Th2细胞相似的细胞因子谱,称为Tc1和Tc2。动物研究的证据表明,CD8(+) T细胞能够通过诱导树突状细胞产生IL-12和IL-18来调节IgE的产生,并且CD8(+) T细胞可能在过敏性致敏过程中作用于局部淋巴结内的Th2极化调节。这些发现提示,诱导Th1极化、CD8(+) T细胞的疫苗会抑制气道高反应性(AHR)和Th2细胞浸润的发展。尽管有这些积极的发现,但肺内CD8(+) T细胞的作用仍了解甚少。虽然CD8(+) T细胞,特别是那些表达Tc1表型的细胞,能够调节炎症并抑制AHR,但据推测,Tc2 CD8(+) T细胞在已确诊的哮喘中占主导地位,可能会放大定义该疾病的不适当免疫反应。在临床上,CD8(+) T细胞与哮喘之间的关联几乎普遍被定义为有害的,这进一步表明这些细胞在已确诊疾病中起有害作用。CD8(+) T细胞可能是治疗干预的一个有价值的潜在靶点,要么通过在致敏发生之前增强其调节作用,要么通过在已确诊的特应性疾病中抑制其促炎特性来实现。