Pinsonneault S, El Bassam S, Mazer B, Cruikshank W W, Laberge S
Hospital Ste-Justine, University of Montreal, Montreal, Canada.
J Allergy Clin Immunol. 2001 Mar;107(3):477-82. doi: 10.1067/mai.2001.112373.
We have previously shown increased expression of the CD4+ cell chemoattractant IL-16 at sites of airway allergic inflammation. Little is known about the significance of IL-16 in allergic inflammation and its role in allergen-driven T-cell cytokine responses. Because IL-16 interacts specifically with CD4+ T cells, we hypothesized that IL-16 released at sites of inflammation may modulate the pattern of cytokines produced by CD4+ T cells.
We investigated the effects of exogenous rhIL-16 on cytokine production of PBMCs from atopic and nonatopic subjects in response to antigen and PHA.
Primary cultures of freshly isolated PBMCs from ragweed-sensitive atopic subjects and nonatopic subjects were stimulated with ragweed or PHA in the presence or absence of rhIL-16. Supernatant levels of IL-4, IL-5, and IFN-gamma were determined by means of ELISA at different time points between 2 and 6 days. Effects of IL-16 on antigen-induced cellular proliferative responses were determined.
No IL-4 protein was detected after antigen stimulation of PBMCs from atopic subjects, whereas significant levels of IL-5 were measured on day 6 (median, 534.9 pg/mL). IL-5 secretion was abolished in PBMC cultures depleted of CD4+ cells. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly reduced the amount of IL-5 released (median, 99.8 pg/mL; P <.001). Detectable levels of IFN-gamma (median, 53.3 pg/mL) were identified after antigen stimulation. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly increased IFN-gamma levels (median, 255.6 pg/mL; P <.05). Effects of rhIL-16 appear to be specific for antigen-stimulated PBMCs in atopic subjects because rhIL-16 did not alter IL-5 or IFN-gamma production in response to PHA nor did rhIL-16 alter cytokine production in nonatopic normal subjects.
These studies suggest that IL-16 can play a role in regulating the production of cytokines seen in allergic states in response to antigen.
我们之前已经表明，在气道变应性炎症部位，CD4+细胞趋化因子白细胞介素-16（IL-16）的表达增加。关于IL-16在变应性炎症中的意义及其在变应原驱动的T细胞细胞因子反应中的作用，人们了解甚少。由于IL-16与CD4+ T细胞特异性相互作用，我们推测在炎症部位释放的IL-16可能会调节CD4+ T细胞产生的细胞因子模式。
我们研究了外源性重组人IL-16（rhIL-16）对特应性和非特应性受试者外周血单核细胞（PBMC）在抗原和PHA刺激下细胞因子产生的影响。
用豚草或PHA刺激从豚草敏感的特应性受试者和非特应性受试者新鲜分离的PBMC原代培养物，同时存在或不存在rhIL-16。在2至6天的不同时间点，通过酶联免疫吸附测定法（ELISA）测定白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和干扰素-γ（IFN-γ）的上清液水平。测定IL-16对抗原诱导的细胞增殖反应的影响。
特应性受试者的PBMC经抗原刺激后未检测到IL-4蛋白，而在第6天检测到显著水平的IL-5（中位数为534.9 pg/mL）。在去除CD4+细胞的PBMC培养物中，IL-5分泌被消除。在抗原刺激的PBMC培养物中添加rhIL-16显著降低了IL-5的释放量（中位数为99.8 pg/mL；P<.001）。抗原刺激后可检测到IFN-γ水平（中位数为53.3 pg/mL）。在抗原刺激的PBMC培养物中添加rhIL-16显著提高了IFN-γ水平（中位数为255.6 pg/mL；P<.05）。rhIL-16的作用似乎对特应性受试者中抗原刺激的PBMC具有特异性，因为rhIL-16不会改变PBMC对PHA刺激的IL-5或IFN-γ产生，rhIL-16也不会改变非特应性正常受试者的细胞因子产生。
这些研究表明，IL-16在调节变应性状态下对抗原产生的细胞因子产生中可能发挥作用。
