Sharma S A, Miller G G, Perez-Perez G I, Gupta R S, Blaser M J
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2605.
Clin Exp Immunol. 1994 Jul;97(1):126-32. doi: 10.1111/j.1365-2249.1994.tb06590.x.
Helicobacter pylori is a major cause of chronic antral gastritis and peptic ulcer disease. Further definition is needed of the factors that determine whether infected individuals remain asymptomatic, or ultimately develop ulceration of the mucosa or transformation to malignancy. To explore the possibility that host response to H. pylori may play a role in the outcome of this infection, we have examined humoral and cellular recognition of several H. pylori proteins by seropositive and seronegative persons. A complex mixture of water-extractable cell proteins, which did not include lipopolysaccharide (LPS), was recognized by serum antibodies only in seropositive or infected individuals. IgG from seropositive subjects also bound to urease and to a heat shock protein (hsp)60 that is homologous to the 65-kD mycobacterial heat shock protein, while sera from uninfected individuals were negative. Although antibody responses to these antigens were restricted to seropositive subjects, T cell recognition of the same proteins was found in both seropositive and seronegative subjects. The water extract of H. pylori stimulated peripheral blood mononuclear cells (PBMC) from all subjects, while purified proteins activated lymphocytes of only some seropositive and seronegative subjects. PBMC that were activated by the H. pylori hsp60 did not respond to the autologous human p60 heat shock protein. These results demonstrate that, in contrast to antibody responses, T cell recognition of H. pylori proteins may occur in non-infected persons. In addition, the data suggest that in these subjects, peripheral lymphocytes that are activated by bacterial heat shock proteins do not mediate tissue damage by recognition of human heat shock homologues.
幽门螺杆菌是慢性胃窦炎和消化性溃疡病的主要病因。对于决定感染个体是保持无症状,还是最终发展为黏膜溃疡或恶变的因素,还需要进一步明确。为了探究宿主对幽门螺杆菌的反应是否可能在这种感染的转归中起作用,我们检测了血清阳性和血清阴性个体对几种幽门螺杆菌蛋白的体液和细胞识别情况。一种不包括脂多糖(LPS)的可水提取细胞蛋白的复杂混合物,仅在血清阳性或感染个体中被血清抗体识别。血清阳性受试者的IgG也与脲酶以及一种与65-kD分枝杆菌热休克蛋白同源的热休克蛋白(hsp)60结合,而未感染个体的血清则为阴性。尽管对这些抗原的抗体反应仅限于血清阳性受试者,但在血清阳性和血清阴性受试者中均发现了对相同蛋白的T细胞识别。幽门螺杆菌的水提取物刺激了所有受试者的外周血单核细胞(PBMC),而纯化蛋白仅激活了一些血清阳性和血清阴性受试者的淋巴细胞。被幽门螺杆菌hsp60激活的PBMC对自身人p60热休克蛋白无反应。这些结果表明,与抗体反应不同,未感染个体也可能发生对幽门螺杆菌蛋白的T细胞识别。此外,数据表明,在这些受试者中,被细菌热休克蛋白激活的外周淋巴细胞不会通过识别人类热休克同源物来介导组织损伤。