Université Paris-Sud, INSERM UMR 996, UFR Pharmacie, Châtenay-Malabry, France.
Allergy. 2013 Jul;68(7):899-905. doi: 10.1111/all.12173. Epub 2013 Jun 10.
Drug hypersensitivity is known to rely on a drug-specific T-cell response. Amplitude of antigen-specific T-cell response is partly controlled by the size of the antigen-specific naïve CD4(+) T-cell repertoire, but estimate of this repertoire has never been investigated for allergenic drugs. The purpose of this study was to evaluate the frequency of benzylpenicillin-specific CD4(+) T lymphocytes in healthy donors.
Co-cultures were established with CD4(+) T lymphocytes from healthy donors and mature autologous dendritic cells loaded with benzylpenicillin coupled to human serum albumin. CD4(+) T lymphocytes were stimulated once a week for 4 weeks with benzylpenicillin coupled to human serum albumin. The CD4(+) T-cell response was measured using an interferon-γ ELISPOT assay. Frequency of benzylpenicillin-specific naive CD4(+) T lymphocytes was then calculated using the Poisson distribution law.
Results showed the presence of benzylpenicillin-specific CD4(+) T lymphocytes in 9 of 10 tested healthy donors irrespective of their HLA typing, with a mean frequency of 0.29 cells per million of CD4(+) T cells. Experiments performed on naive (CD45RA(+) ) and on memory (CD45RO(+) ) CD4(+) T lymphocytes showed that these benzylpenicillin-specific CD4(+) T lymphocytes belonged to the naive T-cell subpopulation.
This study showed for the first time the existence of naive CD4(+) T lymphocytes specific to benzylpenicillin in healthy donors.
已知药物过敏反应依赖于药物特异性 T 细胞反应。抗原特异性 T 细胞反应的幅度部分受抗原特异性初始 CD4(+) T 细胞库的大小控制，但尚未对变应原性药物的这种库进行估计。本研究的目的是评估健康供体中苄青霉素特异性 CD4(+) T 淋巴细胞的频率。
用成熟的自体树突状细胞负载与人血清白蛋白偶联的苄青霉素与健康供体的 CD4(+) T 淋巴细胞共培养。CD4(+) T 淋巴细胞每周用与人血清白蛋白偶联的苄青霉素刺激一次，共刺激 4 周。用干扰素-γ ELISPOT 测定法测量 CD4(+) T 细胞反应。然后使用泊松分布定律计算苄青霉素特异性初始 CD4(+) T 淋巴细胞的频率。
结果显示，10 名测试的健康供体中均存在苄青霉素特异性 CD4(+) T 淋巴细胞，而不论其 HLA 分型如何，平均每百万个 CD4(+) T 细胞中有 0.29 个细胞。在初始（CD45RA(+)）和记忆（CD45RO(+)）CD4(+) T 淋巴细胞上进行的实验表明，这些苄青霉素特异性 CD4(+) T 淋巴细胞属于初始 T 细胞亚群。
本研究首次显示健康供体中存在对苄青霉素特异性的初始 CD4(+) T 淋巴细胞。
