Kawashima Tetsuo, Norose Yoshihiko, Watanabe Yoshiyuki, Enomoto Yutaka, Narazaki Hidehiko, Watari Eiji, Tanaka Shigeo, Takahashi Hidemi, Yano Ikuya, Brenner Michael B, Sugita Masahiko
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
J Immunol. 2003 Jun 1;170(11):5345-8. doi: 10.4049/jimmunol.170.11.5345.
MHC class I-restricted CD8(+) T cells are a crucial component of the host defense against mycobacterial infection in mice, but it has often proved very difficult to identify the CD8 T cell response in humans. Human group 1 CD1 molecules (CD1a, -b, -c) mediate MHC-independent presentation of mycobacteria-derived lipid and glycolipid Ags to CD8(+) T cells, and their intracellular localization to the endocytic system may favor efficient monitoring of phagosome-resident mycobacteria. Here, we show that bacillus Calmette-Guérin (BCG)-immunized subjects contain a significant circulating pool of CD8(+) T cells that recognize BCG-infected DCs in a CD1-dependent, but MHC-independent, manner. These CD1-restricted T cells efficiently detected live, rather than dead, BCG and produced IFN-gamma, an important cytokine for protection against mycobacterial infection. These results emphasize that lipid-reactive CD8(+) T cells may contribute to host defense against mycobacterial infection.
MHC I类限制性CD8(+) T细胞是小鼠宿主抵御分枝杆菌感染的关键组成部分，但在人类中鉴定CD8 T细胞反应往往非常困难。人类1类CD1分子（CD1a、-b、-c）介导分枝杆菌衍生的脂质和糖脂抗原以不依赖MHC的方式呈递给CD8(+) T细胞，并且它们在内吞系统中的细胞内定位可能有利于对吞噬体中驻留的分枝杆菌进行有效监测。在此，我们表明，卡介苗（BCG）免疫的受试者含有大量循环的CD8(+) T细胞池，这些细胞以依赖CD1但不依赖MHC的方式识别BCG感染的树突状细胞（DC）。这些受CD1限制的T细胞能有效检测活的而非死的BCG，并产生γ干扰素，这是一种对抗分枝杆菌感染的重要细胞因子。这些结果强调，脂质反应性CD8(+) T细胞可能有助于宿主抵御分枝杆菌感染。
