Type II pneumocyte-CD8+ T-cell interactions. Relationship between target cell cytotoxicity and activation.
Type II pneumocyte-CD8+ T-cell interactions. Relationship between target cell cytotoxicity and activation.
复制标题
II 型肺细胞-CD8 T 细胞相互作用。
DOI：
10.1165/ajrcmb.25.3.4476
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Enelow,RI
中科院分区：
文献类型：
--
作者：
Zhao,MQ;Amir,MK;Rice,WR;Enelow,RI
CD8 + T-cell responses play an important role in the clearance of respiratory virus infection, but may also contribute to lung injury in the process. The effector mechanisms involved in viral clearance and associated lung injury include both cytolytic and noncytolytic effector functions. Previously we have shown that CD8 + T-cell recognition of alveolar epithelial cells triggers chemokine expression by the epithelial cell and that this plays an important role in the inflammatory infiltration that ensues in the context of T cell–mediated injury (Zhao and colleagues,J. Clin. Invest.2000;106:R49–R58). In the present study we sought to understand the relationship between alveolar cell cytotoxicity and chemokine expression, both of which occur as a result of CD8 + T-cell antigen recognition. Alveolar epithelial cells efficiently process and present overlapping viral epitopes, and CD8 + T-cell recognition of these class I major histocompatibility complex–restricted epitopes resulted in cytotoxicity of the alveolar cells by both wild-type and perforin-deficient T cells. However, the contribution of perforin-mediated lysis to the total cytotoxicity of alveolar cells by CD8 + T cells was minimal, and the majority of the lysis was attributable to tumor necrosis factor- α expressed by the T cell. CD8 + T-cell recognition also led to activation of nuclear factor- κ B in the alveolar epithelial target cells, at levels inversely proportional to the effector/target (E:T) ratio. Finally, at varying E:T ratios, we demonstrated an inverse relationship between alveolar cell cytotoxicity and monocyte chemotactic protein-1 expression, both of which occur as a result of T-cell recognition. These findings may have important ramifications in understanding the relationship between viral clearance and lung injury.
