Evidence for increased expression of regulatory cytokine receptors interleukin-12R and interleukin-18R in common variable immunodeficiency
Evidence for increased expression of regulatory cytokine receptors interleukin-12R and interleukin-18R in common variable immunodeficiency
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DOI：
10.1046/j.1365-2249.2003.02271.x
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发表时间：
2003-11-01
影响因子：
4.6
通讯作者：
Bofill, M
中科院分区：
文献类型：
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作者：
McQuaid, A;Tormey, VJ;Bofill, M
我们研究了常见可变免疫缺陷(CVID)患者淋巴细胞上T辅助(Th)1/Th2调节细胞因子受体的表达，并将结果与健康人和特应性哮喘患者(后者通常被认为是Th2驱动的疾病)的结果进行了比较。我们认为一些相关受体的改变可能与观察到的Th1/Th2细胞因子失衡有关。CVID患者CD212[IL-12Rbeta1]细胞在CD4(+)CD45RA(+)和CD8(+)CD45RA(+)亚群中所占比例(分别为24%和41%)高于健康人(分别为6%和23%)。约21%的CD4(+)CD45RA(+)初始细胞表达IL-18Rpha，而健康受试者的这一比例为11%。相反，哮喘患者细胞因子受体的表达与对照组相似。尽管存在上述差异，但经抗CD3和抗CD28刺激72 h后，三组细胞因子受体表达上调情况相似，高达80%的CD45RA(+)和CD45RO(+)淋巴细胞表达CD212(IL-12Rbeta1)和IL-18Rpha。大约50%的“幼稚”和25%的“记忆”亚群上调IL-12Rbeta2。这些发现为CVID患者Th1免疫反应的两极化提供了进一步的证据，其机制可能涉及IL-12介导的通路上调。
We investigated the expression of T helper (Th)1/Th2 regulatory cytokine receptors on lymphocytes from patients with common variable immunodeficiency (CVID), a disorder associated with raised Th1 cytokine production, comparing the results with those from healthy individuals and atopic asthmatics, the latter generally considered to have a Th2-driven disease. We proposed that alterations in some of the relevant receptors might be related to the observed imbalances in Th1/Th2 cytokines. Cells from CVID patients showed an increase in the percentages of CD212 [interleukin (IL)-12Rbeta1] cells within the CD4(+) CD45RA(+) and CD8(+) CD45RA(+) subsets (24% and 41%, respectively), as compared to CD4(+) CD45RA(+) and CD8(+) CD45RA(+) in healthy subjects (6% and 23%, respectivey). Approximately 21% of the CD4(+) CD45RA(+) naive cells expressed IL-18Ralpha, compared with 11% in healthy subjects. In contrast, the cytokine-receptor expression in asthmatics was similar to that of controls. In spite of the above differences, after 72 h of stimulation with anti-CD3 and anti-CD28, cytokine receptor up-regulation was similar in all three groups, with up to 80% of both CD45RA(+) and CD45RO(+) lymphocytes expressing CD212 (IL-12Rbeta1) and IL-18Ralpha. Approximately 50% of the 'naive', and 25% of the 'memory' subpopulations up-regulated IL-12Rbeta2. These findings provide further evidence of a polarization towards a Th1 immune response in CVID, the mechanism possibly involving up-regulation of IL-12-mediated pathways.