Induction of CD8 T cells against a novel epitope in TB10.4: Correlation with mycobacterial virulence and the presence of a functional region of difference-1
Induction of CD8 T cells against a novel epitope in TB10.4: Correlation with mycobacterial virulence and the presence of a functional region of difference-1
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DOI：
10.4049/jimmunol.179.6.3973
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Dietrich, Jes
中科院分区：
文献类型：
--
作者：
Billeskov, Rolf;Vingsbo-Lundberg, Carina;Dietrich, Jes
尽管结核分枝杆菌（Mycobacterium tuberculosis，M.tb）感染诱导了强烈的CD 8 T细胞应答，但CD 8 T细胞在防御M.tb中的作用以及诱导CD 8 T细胞的机制仍然不清楚。TB10.4是最近描述的由卡介苗（BCG）和结核分枝杆菌（M. tb）两者表达的Ag。在本研究中，我们描述了TB10.4中的一种新的CD 8 T细胞表位，TB10.4（3-11）。我们发现TB10.4（3-11）特异性CD 8 T细胞在感染开始时被诱导，并在整个感染过程中大量存在。将TB10.4（3-11）CD 8 T细胞募集至感染部位并表达CD 44、TNF-α和IFN-γ。此外，TB 10 A（3-11）CD 8 T细胞显示FasL和LAMP-1/2（CD 107 A/B）的上调，这与强的体内细胞溶解活性相关。与用M. tb感染相比，用BCG感染后TB 10.4（3-11）特异性CD 8 T细胞的诱导不太明显。通过使用表达遗传差异区-1（RD 1）的rBCG，我们表明功能性RD 1区的存在增加了TB10.4（3-11）特异性CD 8 T细胞的诱导以及细菌毒力。最后，由于缺乏遗传区域RD 1的结核分枝杆菌变体也诱导了大量的TB 10.4（3-11）特异性CD 8 T细胞，并且与BCG相比表现出更高的毒力，我们的数据表明，毒力本身也参与产生针对分枝杆菌表位（如TB 10.4（3-11））的强大CD 8 T细胞应答。
Although infection with Mycobacterium tuberculosis (M.tb) induces a robust CD8 T cell response, the role of CD8 T cells in the defense against M.tb, and the mechanisms behind the induction of CD8 T cells, is still not clear. TB10.4 is a recently described Ag that is expressed by both bacillus Calmette-Guerin (BCG) and M.tb. In the present study, we describe a novel CD8 T cell epitope in TB10.4, TB10.4(3-11). We show that TB10.4(3-11)-specific CD8 T cells are induced at the onset of infection and are present throughout the infection in high numbers. TB10.4(3-11) CD8 T cells were recruited to the site of infection and expressed CD44, TNF-alpha, and IFN-gamma. In addition, TB10A(3-11) CD8 T cells showed an up-regulation of FasL and LAMP-1/2 (CD107A/B), which correlated with a strong in vivo cytolytic activity. The induction of TB 10.4(3-11)-specific CD8 T cells was less pronounced following infection with BCG compared to infection with M.tb. By using a rBCG expressing the genetic region of difference-1 (RD1), we show that the presence of a functional RD1 region increases the induction of TB10.4(3-11)-specific CD8 T cells as well as the bacterial virulence. Finally, as an M.tb variant lacking the genetic region RD1 also induced a significant amount of TB 10.4(3-11)-specific CD8 T cells, and exhibited increased virulence compared with BCG, our data suggest that virulence in itself is also involved in generating a robust CD8 T cell response against mycobacterial epitopes, such as TB10.4(3-11).