Cornejo-Garcia J A, Fernandez T D, Torres M J, Carballo M, Hernan I, Antunez C, Blanca M, Mayorga C
Research Laboratory for Allergic Diseases, Carlos Haya Hospital-Fundacion IMABIS, Málaga, Spain.
Allergy. 2007 Dec;62(12):1429-38. doi: 10.1111/j.1398-9995.2007.01542.x.
Allergic drug reactions (ADR) can be either immediate reaction (IR) (IgE mediated) or delayed reaction (DR) (T-cell mediated). They follow the Th1/Th2 paradigm, with DR expressing interferon-gamma (IFN-gamma) with down-regulation of interleukin-4 (IL-4) and IR expressing IL-4 with down-regulation of IFN-gamma. We studied the extension of this polarization in DR and IR by examining the cytokine and transcription factor profile in T-cell subpopulations during the acute phase of an ADR.
Expressions of cytokines [IL-4, IFN-gamma and tumor necrosis factor-alpha (TNF-alpha)] and transcription factors (c-maf, GATA-3 and T-bet) were analysed by semi-quantitative real time-polymerase chain reaction in peripheral blood mononuclear cells and in CD4 and CD8 subpopulations from ADR patients.
In DR, IFN-gamma, TNF-alpha and T-bet increased significantly in both CD4 and CD8 subpopulations, depending on the clinical severity. In IR, IL-4, c-Maf and GATA-3 were increased, but only significantly in CD4. A positive correlation existed between IFN-gamma and T-bet in DR and between IL-4 and c-Maf and GATA-3 in IR. In DR, IFN-gamma, TNF-alpha and T-bet were increased during the acute phase in CD4 and CD8. In IR, IL-4, c-Maf and GATA-3 were all increased in the acute phase, but only in CD4.
These results support the Th1/Th2 paradigm in ADR, confirming previous findings that include the expression in both CD4 and CD8 T cells, and extending the observation to the transcription factors involved in the polarization of the immune response. Monitoring the reactions in the cell populations implicated, could be an important tool for assessing the mechanisms involved in ADR.
药物过敏反应（ADR）可分为速发型反应（IR）（IgE介导）或迟发型反应（DR）（T细胞介导）。它们遵循Th1/Th2模式，DR表现为干扰素-γ（IFN-γ）表达且白细胞介素-4（IL-4）下调，而IR表现为IL-4表达且IFN-γ下调。我们通过检测ADR急性期T细胞亚群中的细胞因子和转录因子谱，研究了DR和IR中这种极化现象的扩展情况。
采用半定量实时聚合酶链反应分析ADR患者外周血单个核细胞以及CD4和CD8亚群中细胞因子[IL-4、IFN-γ和肿瘤坏死因子-α（TNF-α）]和转录因子（c-maf、GATA-3和T-bet）的表达。
在DR中，根据临床严重程度，CD4和CD8亚群中的IFN-γ、TNF-α和T-bet均显著增加。在IR中，IL-4、c-Maf和GATA-3增加，但仅在CD4中显著增加。DR中IFN-γ与T-bet之间以及IR中IL-4与c-Maf和GATA-3之间存在正相关。在DR中，急性期CD4和CD8中的IFN-γ、TNF-α和T-bet增加。在IR中，急性期IL-4、c-Maf和GATA-3均增加，但仅在CD4中增加。
这些结果支持ADR中的Th1/Th2模式，证实了先前包括CD4和CD8 T细胞中表达的发现，并将观察扩展到免疫反应极化所涉及的转录因子。监测相关细胞群体中的反应，可能是评估ADR所涉及机制的重要工具。
