TH1-TYPE RESPONSES BY HUMAN T CELLS STIMULATED BY BRUCELLA ABORTUS

由于我们考虑将流产布鲁氏菌(BA)作为人类 疫苗，特别是对艾滋病毒-1感染者，重要的是要知道 它对人类T细胞有什么影响。来自老鼠研究的证据， 在体内进行，表明反复注射BA会导致干扰素- γ(IFNy)释放和扩增TH1细胞。我们发现人类T细胞 流式细胞术检测CD3+细胞(85-95%)对BA和 BA产生的脂多糖(LPS)。这种对BA的反应增加了 在IL-2存在的情况下协同作用。CD4+和CD8+T细胞， 通过摇摄分离，当BA刺激时释放IFNy。T细胞来源 HIV-1感染的无张力人群也能够对BA和 秘而不宣。然而，来自有症状患者的T细胞只是 如果存在IL-2，则有反应。IFNY已被证明是TH1的产物 细胞，IL-4的分泌，这是TH2细胞的功能，用 BA刺激的细胞株(CtH4)不能诱导其增殖。 CtH4，对10pg/mlIL-4敏感。同样地， 在这些上清液中没有检测到IL-4，这是 对30pg/ml的IL-4敏感。这些结果被聚合酶链式反应证实。 分析表明，BA可诱导IFNy，但不能诱导IL-4mRNA的表达。这些数据 提示BA产生的BA内毒素能够选择性地刺激人 Th1细胞。这对疫苗开发具有重要意义，因为 Th1细胞偏向可能对某些感染提供更好的保护 包括HIV-1。

Since we are considering Brucella abortus (BA) as a carrier for human vaccines, especially for HIV-1 infected persons, it was important to know what effect it had on human T cells. Evidence from murine studies, performed in vivo, suggested that repeated BA injections caused interferon- gamma (IFNy) release and expansion of TH1 cells. We found that human T cells (85-95% CD3+ by flow cytometry) secred IFNy in response to BA and lipopolysaccharide (LPS) from BA. This response to BA was increased synergistically in the presence of IL-2. Both CD4+ and CD8+ T cells, separated by panning, released IFNy when stimulated by BA. T cells from HIV-1 infected asympotmatic persons were also able to respond to BA and secrete IFNy. However, T cells from patients with symptoms were only responsive if IL-2 was present. IFNy has been shown to be a product of TH1 cells, IL-4 secretion, which is a function of TH2 cells, was assessed using a cell line (CtH4), cells stimulated by BA did not induce proliferation of CtH4, which was sensitive to the presence of 10 pg/ml of IL-4. Similarily, no IL-4 was detected in these supernatants in the ELISA, which was sensitive to 30 pg/ml of IL-4. These results were confirmed by PCR analysis, which showed that BA induced IFNy, but not IL-4 mRNA. These data suggest that BA LPS from BA are capable of selectively stimulating human TH1 cells. This has important implications in vaccine development since a TH1 cell bias may afford greater protection against certain infections including HIV-1.