Thottingal Tina B, Stefura Bill P, Simons F Estelle R, Bannon Gary A, Burks Wesley, HayGlass Kent T
Department of Immunology, University of Manitoba, Winnipeg, Canada.
J Allergy Clin Immunol. 2006 Oct;118(4):905-14. doi: 10.1016/j.jaci.2006.06.016. Epub 2006 Aug 24.
Peanut allergy is a major cause of anaphylaxis. Regulation of immune responses to peanut allergen, particularly why sensitization does not usually progress to allergic reactions, is not well investigated. Most studies focus exclusively on serologic responses and individuals with peanut allergy.
We sought to determine the existence, prevalence, and nature of peanut-specific, T cell-dependent cytokine and chemokine responses of adults who eat peanut without having symptoms.
We developed systems to examine specific immunity in peanut-tolerant individuals who had (1) negative histories and negative peanut skin test responses, (2) negative histories and positive peanut skin test responses, and (3) clinically apparent peanut allergy. After primary culture of PBMCs restimulated with whole peanut extract, we quantified responses characteristic of TH1 (IFN-gamma and CXCL10) and TH2-like immunity (IL-5, IL-13, CCL17, and CCL22) using ultrasensitive ELISAs. Antigen-presenting cell costimulatory requirements (CD4, HLA-DR, CD80/86, and cytotoxic T lymphocyte-associated antigen 4 [CTLA4] Ig) were determined.
T cell-dependent, peanut-specific IL-5, IL-13, and CCL22 were common in peanut-tolerant individuals, regardless of whether they had positive or negative skin test responses. These were blocked by anti-CD4 and were dependent on CD28/CD86 costimulation. None of the 70 individuals studied had demonstrable IFN-gamma or CXCL10 responses to peanut. All demonstrated TH1 and TH2 responses to the ubiquitous recall antigen streptokinase.
Qualitatively similar and quantitatively increasing peanut-specific TH2 responses in the consistent absence of putatively protective TH1 immunity were found in both peanut-tolerant individuals and those with peanut allergy.
The continuum of responses between individuals with negative and individuals with positive skin test results, rather than TH1 versus TH2 bias, might be important in peanut allergy.
花生过敏是过敏反应的主要原因。对花生过敏原免疫反应的调节，尤其是致敏通常为何不会发展为过敏反应，尚未得到充分研究。大多数研究仅专注于血清学反应和花生过敏个体。
我们试图确定食用花生但无症状的成年人中花生特异性、T细胞依赖性细胞因子和趋化因子反应的存在、患病率及性质。
我们开发了系统来检测花生耐受个体的特异性免疫，这些个体包括：（1）病史阴性且花生皮肤试验反应阴性；（2）病史阴性且花生皮肤试验反应阳性；（3）临床明显的花生过敏。在用全花生提取物再次刺激外周血单核细胞（PBMCs）进行原代培养后，我们使用超灵敏酶联免疫吸附测定法（ELISA）对TH1（干扰素-γ和CXCL10）和TH2样免疫（白细胞介素-5、白细胞介素-13、CCL17和CCL22）的特征性反应进行定量。确定抗原呈递细胞共刺激需求（CD4、人类白细胞抗原-DR、CD80/86和细胞毒性T淋巴细胞相关抗原4 [CTLA4] 免疫球蛋白）。
T细胞依赖性、花生特异性白细胞介素-5、白细胞介素-13和CCL22在花生耐受个体中很常见，无论其皮肤试验反应是阳性还是阴性。这些反应被抗CD4阻断，并依赖于CD28/CD86共刺激。所研究的70名个体中，没有一人对花生表现出可检测到的干扰素-γ或CXCL10反应。所有人对普遍存在的回忆抗原链激酶都表现出TH1和TH2反应。
在花生耐受个体和花生过敏个体中均发现，在假定的保护性TH1免疫持续缺失的情况下，花生特异性TH2反应在质量上相似且在数量上增加。
皮肤试验结果阴性和阳性个体之间的反应连续体，而非TH１与TH2偏差，可能在花生过敏中起重要作用。
