Emoto M, Danbara H, Yoshikai Y
Laboratory of Germfree Life, Nagoya University School of Medicine, Japan.
J Exp Med. 1992 Aug 1;176(2):363-72. doi: 10.1084/jem.176.2.363.
To elucidate the relationship between the virulence of intracellular bacterium and its ability to induce gamma/delta T cells in the host during infection, we examined the differences in appearance of gamma/delta T cells in mice infected with Salmonella choleraesuis virulent strain RF-1 carrying a virulence plasmid of 50 kb, and with avirulent strain 31N-1 cured of the 50-kb plasmid. The number of gamma/delta T cells in the peritoneal cavity was increased to a significant level on day 3 after an intraperitoneal infection with a sublethal dose (5 x 10(4) colony-forming units) of avirulent strain 31N-1. On the other hand, no increase in the number of gamma/delta T cells was evident in the peritoneal cavity at any stage after infections with various doses of virulent strain RF-1, although the numbers of the bacteria were drastically increased. Similar to that seen in the peritoneal cavity, the number of gamma/delta T cells in the liver was significantly increased after an intraperitoneal infection with avirulent strain 31N-1 but not with virulent strain RF-1. The early appearing gamma/delta T cells during salmonellosis with avirulent stain 31N-1, which preferentially used V gamma 1/V delta 6, showed blastogenesis in response to purified protein derivative (PPD) derived from Mycobacterium tuberculosis. The gamma/delta T cells also responded to the peritoneal adherent cells in mice infected with avirulent strain 31N-1 6 d previously, which expressed a high level of endogenous heat-shock protein (hsp) homologous to the mycobacterial 65-kD hsp. The expression of the hsp, however, was not prominent in the adherent cells in mice infected with virulent strain RF-1. These results suggest that the gamma/delta T cells specific for PPD may play important roles in host defense against murine salmonellosis, and that the virulence of Salmonella may be inversely correlated with its ability to induce endogenous hsp in the infected macrophages, which in turn stimulate the gamma/delta T cells in the host during salmonellosis.
为阐明细胞内细菌的毒力与其在感染期间诱导宿主γ/δ T细胞能力之间的关系，我们检测了感染携带50 kb毒力质粒的猪霍乱沙门氏菌强毒株RF-1和已治愈50 kb质粒的无毒株31N-1的小鼠中γ/δ T细胞出现情况的差异。用亚致死剂量（5×10⁴集落形成单位）的无毒株31N-1腹腔感染小鼠后第3天，腹腔内γ/δ T细胞数量显著增加。另一方面，用不同剂量的强毒株RF-1感染后，尽管细菌数量急剧增加，但在任何阶段腹腔内γ/δ T细胞数量均无明显增加。与腹腔内情况相似，用无毒株31N-1腹腔感染后肝脏中γ/δ T细胞数量显著增加，而用强毒株RF-1感染后则未增加。在感染无毒株31N-1的沙门氏菌病早期出现的γ/δ T细胞，优先使用Vγ1/Vδ6，对结核分枝杆菌来源的纯化蛋白衍生物（PPD）有增殖反应。这些γ/δ T细胞也对6天前感染无毒株31N-1的小鼠腹腔黏附细胞有反应，这些黏附细胞表达高水平的与分枝杆菌65-kD热休克蛋白（hsp）同源的内源性热休克蛋白。然而，在感染强毒株RF-1的小鼠黏附细胞中，hsp的表达并不显著。这些结果表明，对PPD特异的γ/δ T细胞可能在宿主抵抗鼠伤寒沙门氏菌病中发挥重要作用，并且沙门氏菌的毒力可能与其在感染巨噬细胞中诱导内源性hsp的能力呈负相关，而内源性hsp又在沙门氏菌病期间刺激宿主中的γ/δ T细胞。
