Kuerten Stefanie, Schlingmann Tobias R, Rajasalu Tarvo, Angelov Doychin N, Lehmann Paul V, Tary-Lehmann Magdalena
Institut für Anatomie I, Medizinische Fakultät der Universität zu Köln, Joseph-Stelzmann-Str. 9, 50931 Köln, Germany.
Clin Dev Immunol. 2008;2008:590941. doi: 10.1155/2008/590941.
Measurements of antigen-specific T cell responses in chronic diseases are limited by low frequencies of antigen-specific cells in the peripheral blood. Therefore, attempts have been made to add costimulatory molecules such as anti-CD28 or IL-7/IL-15 to ELISPOT assays to increase sensitivity. While this approach has been successful under certain circumstances, results are often inconsistent. To date, there are no comprehensive studies directly comparing the in vitro effects of multiple costimulatory molecules in different disease settings. Therefore, in the present study we tested the effects of IL-7/IL-15, IFN-alpha, anti-ICOS, and anti-CD28 on antigen-specific T cell responses in patients infected with HCV or HIV versus healthy individuals. Our data show that none of the aforementioned molecules could significantly increase ELISPOT sensitivity, neither in HCV nor in HIV. Moreover, all of them caused false-positive responses to HCV and HIV antigens in healthy individuals. Our results question the broad use of in vitro costimulation.
慢性疾病中抗原特异性T细胞反应的测量受到外周血中抗原特异性细胞低频率的限制。因此,人们尝试在ELISPOT检测中添加共刺激分子,如抗CD28或IL-7/IL-15,以提高灵敏度。虽然这种方法在某些情况下取得了成功,但结果往往不一致。迄今为止,尚无直接比较多种共刺激分子在不同疾病背景下体外效应的全面研究。因此,在本研究中,我们测试了IL-7/IL-15、IFN-α、抗ICOS和抗CD28对丙型肝炎病毒(HCV)或人类免疫缺陷病毒(HIV)感染患者与健康个体中抗原特异性T细胞反应的影响。我们的数据表明,上述分子均不能显著提高ELISPOT的灵敏度,无论是在HCV感染患者还是HIV感染患者中。此外,所有这些分子都在健康个体中引起了对HCV和HIV抗原的假阳性反应。我们的结果对体外共刺激的广泛应用提出了质疑。