Marcondes Maria Cecilia G, Burdo Tricia H, Sopper Sieghart, Huitron-Resendiz Salvador, Lanigan Caroline, Watry Debbie, Flynn Claudia, Zandonatti Michelle, Fox Howard S
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Immunol. 2007 May 1;178(9):5812-9. doi: 10.4049/jimmunol.178.9.5812.
The host reaction to infection of the brain contributes to a number of CNS pathologies including neuro-AIDS. In this study, we have identified the accumulation of SIV-specific CTL in the brains of SIV-infected animals who have neurophysiological abnormalities but are otherwise asymptomatic. SIV-specific CTL enter the brain early after viral infection and are maintained in the brain even when those reactive with an immunodominant epitope in Tat are lost from the rest of the body. The specialized CNS environment contributes to this unique outcome. Following SIV infection, brain levels of IL-15 were significantly elevated whereas IL-2 was absent, creating an environment that favors CTL persistence. Furthermore, in response to IL-15, brain-derived CD8(+) T cells could expand in greater numbers than those from spleen. The accumulation, persistence, and maintenance of CTL in the brain are closely linked to the increased levels of IL-15 in the absence of IL-2 in the CNS following SIV infection.
宿主对脑部感染的反应会导致包括神经艾滋病在内的多种中枢神经系统病变。在本研究中，我们发现在感染了猴免疫缺陷病毒（SIV）的动物脑部，存在SIV特异性细胞毒性T淋巴细胞（CTL）的聚集，这些动物虽有神经生理异常，但并无其他症状。SIV特异性CTL在病毒感染后早期进入脑部，即便那些与Tat蛋白中免疫显性表位发生反应的CTL从身体其他部位消失，它们仍能在脑部留存。特殊的中枢神经系统环境导致了这一独特结果。感染SIV后，脑部白细胞介素-15（IL-15）水平显著升高，而白细胞介素-2（IL-2）缺失，从而营造了有利于CTL持续存在的环境。此外，对IL-15作出反应时，脑源性CD8(+) T细胞比脾源性CD8(+) T细胞能大量扩增。SIV感染后，中枢神经系统中IL-2缺失而IL-15水平升高，这与CTL在脑部的聚集、留存及维持密切相关。
