Kämmerer R, Chvatchko Y, Kettner A, Dufour N, Corradin G, Spertini F
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Allergy Clin Immunol. 1997 Jul;100(1):96-103. doi: 10.1016/s0091-6749(97)70200-8.
Immunologic mechanisms of desensitization are still incompletely understood. Safer methods of immunotherapy with reduced risks of anaphylaxis need to be developed.
To study the effects of conventional venom immunotherapy (VIT) on phospholipase A2(PLA2)-specific T cells and on T-cell reactivity to short and long synthetic peptides that map the PLA2 molecule.
Proliferation of a CD4+ cell-enriched peripheral blood mononuclear cell fraction and cytokine secretion by T cell lines from patients hypersensitive to bee venom and undergoing VIT in response to PLA2 and PLA2 synthetic peptides were measured.
T-cell proliferation in response to three synthetic peptides, 40 to 60 amino acids long and mapping the entire PLA2 molecule with an overlap of 10 residues (1 to 59, 51 to 99, and 90 to 134) steadily increased during the first 14 weeks of VIT corresponding to the treatment period with incremental doses of antigen. These results are in contrast to the low proliferation indices obtained with short (15 amino acid-long) peptides, and the inability to characterize the immunodominant region of the molecule with short peptides. At the end of VIT (after 3 to 5 years), there was correspondingly, a marked decrease in T cell responsiveness to PLA2 and to its long synthetic peptides. This response was paralleled by a shift in the pattern of cytokine secretion by T cell lines from a T(H0)-type to a T(H1)-type pattern.
After a transient increase in T-cell proliferation, late VIT was characterized by T-cell hyporesponsiveness to allergen and by modulation of cytokine secretion from a T(H0)-type to a T(H1)-type pattern. Because of their capacity to recruit multiple T-cell epitopes, long peptides mapping the entire PLA2 molecule appear to be efficient T cell stimulators and may represent potential candidates for peptide immunotherapy.
脱敏的免疫机制仍未完全明确。需要研发出更安全、过敏反应风险更低的免疫疗法。
研究传统毒液免疫疗法（VIT）对磷脂酶A2（PLA2）特异性T细胞以及T细胞对绘制PLA2分子图谱的长短不同合成肽的反应性的影响。
检测对蜂毒过敏且接受VIT治疗的患者针对PLA2及PLA2合成肽的富含CD4+细胞的外周血单核细胞组分的增殖情况以及T细胞系的细胞因子分泌情况。
在VIT的前14周（对应递增剂量抗原的治疗期），对三种长度为40至60个氨基酸、绘制整个PLA2分子图谱且有10个残基重叠（1至59、51至99以及90至134）的合成肽的T细胞增殖稳步增加。这些结果与短肽（15个氨基酸长）获得的低增殖指数形成对比，且短肽无法确定该分子的免疫显性区域。在VIT结束时（3至5年后），相应地，T细胞对PLA2及其长合成肽的反应性显著降低。这种反应伴随着T细胞系细胞因子分泌模式从T(H0)型向T(H1)型的转变。
在T细胞增殖短暂增加后，晚期VIT的特征是T细胞对变应原反应低下以及细胞因子分泌从T(H0)型向T(H1)型模式的调节。由于能够募集多个T细胞表位，绘制整个PLA2分子图谱的长肽似乎是有效的T细胞刺激剂，可能代表肽免疫疗法的潜在候选物。
