Vallbracht Simone, Unsöld Heike, Ehl Stephan
Children's Hospital, University of Freiburg, Germany.
Eur J Immunol. 2006 Jun;36(6):1434-42. doi: 10.1002/eji.200535642.
We investigated the differentiation phenotype and function of virus-specific and non-specific CTL that were recruited to the lung parenchyma and the bronchoalveolar space after respiratory virus infections. Soon after virus elimination, we observed functional impairment of CTL isolated from the airways in their ability to produce IFN-gamma and TNF-alpha and to lyse target cells. Impaired cytotoxicity was due to a reduced content of granzyme B and a reduced ability to mobilize lytic granules. This impairment in effector functions (a) was largely restricted to CTL in the lung airways, (b) affected both CTL specific for the infecting virus as well as those that were recruited non-specifically to the inflamed lung, (c) was independent of contact between CTL and their specific viral antigen, (d) was not restricted to terminally differentiated CTL but also affected resting memory CTL and (e) could be elicited by both respiratory syncytial virus and influenza virus and thus seemed to be largely independent of the infecting virus. These observations suggest that functional impairment of antiviral T cells in the lung is not the consequence of a viral escape strategy. It may rather result from the particular milieu in the bronchoalveolar space and reflect a host mechanism to prevent excessive pulmonary inflammation.
我们研究了呼吸道病毒感染后募集到肺实质和支气管肺泡腔的病毒特异性和非特异性CTL的分化表型及功能。病毒清除后不久，我们观察到从气道分离的CTL在产生IFN-γ和TNF-α以及裂解靶细胞的能力方面存在功能障碍。细胞毒性受损是由于颗粒酶B含量降低以及动员裂解颗粒的能力下降。效应器功能的这种损伤（a）在很大程度上局限于肺气道中的CTL，（b）影响针对感染病毒的CTL以及非特异性募集到炎症肺组织的CTL，（c）独立于CTL与其特异性病毒抗原之间的接触，（d）不仅限于终末分化的CTL，还影响静息记忆CTL，并且（e）可由呼吸道合胞病毒和流感病毒引发，因此似乎在很大程度上独立于感染病毒。这些观察结果表明，肺中抗病毒T细胞的功能障碍不是病毒逃逸策略的结果。它可能反而源于支气管肺泡腔的特殊环境，并反映了一种防止过度肺部炎症的宿主机制。
