Secrist H, Chelen C J, Wen Y, Marshall J D, Umetsu D T
Department of Pediatrics, Stanford University, California 94305.
J Exp Med. 1993 Dec 1;178(6):2123-30. doi: 10.1084/jem.178.6.2123.
Allergen specific CD4+ T cell clones generated from allergic individuals have been shown to produce increased levels of the cytokine interleukin 4 (IL-4), compared to allergen specific clones generated from nonallergic individuals. This difference between CD4+ T cells from allergic and nonallergic individuals with regard to cytokine production in response to allergen is thought to be responsible for the development of allergic disease with increased IgE synthesis in atopic individuals. We examined the production of IL-4 in subjects with allergic rhinitis and in allergic individuals treated with allergen immunotherapy, a treatment which involves the subcutaneous administration of increasing doses of allergen and which is highly effective and beneficial for individuals with severe allergic rhinitis. We demonstrated that the quantity of IL-4 produced by allergen specific memory CD4+ T cells from allergic individuals could be considerably reduced by in vivo treatment with allergen (allergen immunotherapy). Immunotherapy reduced IL-4 production by allergen specific CD4+ T cells to levels observed with T cells from nonallergic subjects, or to levels induced with nonallergic antigens such as tetanus toxoid. In most cases the levels of IL-4 produced were inversely related to the length of time on immunotherapy. These observations indicate that immunotherapy accomplishes its clinical effects by reducing IL-4 synthesis in allergen specific CD4+ T cells. In addition, these observations indicate that the cytokine profiles of memory CD4+ T cells can indeed be altered by in vivo therapies. Thus, the cytokine profiles of memory CD4+ T cells are mutable, and are not fixed as had been suggested by studies of murine CD4+ memory T cells. Finally, treatment of allergic diseases with allergen immunotherapy may be a model for other diseases which may require therapies that alter inappropriate cytokine profiles of memory CD4+ T cells.
与从非过敏个体产生的变应原特异性克隆相比，从过敏个体产生的变应原特异性CD4 + T细胞克隆已显示出细胞因子白细胞介素4（IL-4）水平升高。过敏个体和非过敏个体的CD4 + T细胞在响应变应原时细胞因子产生方面的这种差异被认为是导致特应性个体中IgE合成增加的过敏性疾病发展的原因。我们检查了过敏性鼻炎患者以及接受变应原免疫疗法治疗的过敏个体中IL-4的产生情况，变应原免疫疗法是一种涉及皮下注射递增剂量变应原的治疗方法，对重度过敏性鼻炎患者非常有效且有益。我们证明，通过变应原体内治疗（变应原免疫疗法），过敏个体的变应原特异性记忆CD4 + T细胞产生的IL-4量可大幅减少。免疫疗法将变应原特异性CD4 + T细胞产生的IL-4降低到非过敏受试者T细胞所观察到的水平，或降低到由破伤风类毒素等非变应原性抗原诱导的水平。在大多数情况下，产生的IL-4水平与免疫疗法的时间长度呈负相关。这些观察结果表明免疫疗法通过减少变应原特异性CD4 + T细胞中的IL-4合成来实现其临床效果。此外，这些观察结果表明记忆CD4 + T细胞的细胞因子谱确实可以通过体内疗法改变。因此，记忆CD4 + T细胞的细胞因子谱是可变的，并不像对小鼠CD4 +记忆T细胞的研究所暗示的那样是固定不变的。最后，用变应原免疫疗法治疗过敏性疾病可能是其他疾病的一个模型，这些疾病可能需要改变记忆CD4 + T细胞不适当细胞因子谱的疗法。
