Khalifeh M S, Stabel J R
Jordan University of Science and Technology, Irbid, Jordan.
Clin Vaccine Immunol. 2013 Aug;20(8):1274-82. doi: 10.1128/CVI.00246-13. Epub 2013 Jun 12.
CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity. In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β. Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic). A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals. The addition of live M. avium subsp. paratuberculosis to cell cultures resulted in downregulation of CD40L expression in naturally infected cows, regardless of the disease stage. In contrast, the addition of live M. avium subsp. paratuberculosis to cultures resulted in upregulation of CD40 expression on cells obtained from clinically infected animals, while a decrease in expression was noted for healthy and subclinically infected cows. No effects of exogenous cytokines on CD40 or CD40L expression were observed. These results clearly point for the first time to a disparity in the expression of these costimulatory molecules on immune cells from cattle in different stages of Johne's disease and suggest further investigation into their roles in paratuberculosis pathogenesis.
CD40和CD40配体（CD40L）作为宿主免疫中一系列复杂事件的一部分，具有共刺激作用。在本研究中，对从患有副结核病的牛分离出的外周血单个核细胞（PBMC）上CD40和CD40L的表达进行了检测，检测对象为新鲜分离的PBMC以及在有或无活副结核分枝杆菌亚种、外源性γ干扰素、白细胞介素10和转化生长因子β存在的情况下培养8、24和72小时的细胞。结果表明，与健康对照动物或处于疾病亚临床阶段（无症状）的奶牛相比，从处于疾病临床阶段（有症状）的动物获得的新鲜PBMC上CD40和CD40L的表达更高。对于培养的PBMC，也观察到了类似的表达模式，但幅度更大，从临床感染动物获得的PBMC在培养8和24小时后CD40表达增加，在24至72小时之间CD40L表达增加。将活副结核分枝杆菌亚种添加到细胞培养物中，导致自然感染奶牛的CD40L表达下调，无论疾病处于哪个阶段。相反，将活副结核分枝杆菌亚种添加到培养物中，导致从临床感染动物获得的细胞上CD40表达上调，而健康和亚临床感染奶牛的表达则下降。未观察到外源性细胞因子对CD40或CD40L表达的影响。这些结果首次明确指出，在副结核病不同阶段的牛免疫细胞上，这些共刺激分子的表达存在差异，并建议进一步研究它们在副结核病发病机制中的作用。
