Agnellini Paola, Wolint Petra, Rehr Manuela, Cahenzli Julia, Karrer Urs, Oxenius Annette
Institute of Microbiology, Eidgenössische Technische Hochschule, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4565-70. doi: 10.1073/pnas.0610335104. Epub 2007 Mar 7.
In persistent viral infections, the host's immune system is challenged by the constant exposure to antigen, potentially causing continuous activation of CD8(+) T cells with subsequent immunopathology. Here we demonstrate, for experimental chronic lymphocytic choriomeningitis virus and human HIV infection, that upon prolonged in vivo exposure to antigen, TCR-triggered Ca(2+) flux, degranulation, and cytotoxicity are maintained on a cellular level, whereas cytokine production is severely impaired because of a selective defect in activation-induced NFAT nuclear translocation. During chronic infection, this differential regulation of pathways leading to diverse effector functions may allow CD8(+) T cells to sustain some degree of local viral control by direct cytotoxicity while limiting systemic immune pathology by silencing cytokine production.
在持续性病毒感染中，宿主免疫系统因持续接触抗原而受到挑战，这可能导致CD8(+) T细胞持续活化，进而引发免疫病理反应。在此，我们针对实验性慢性淋巴细胞性脉络丛脑膜炎病毒感染和人类HIV感染证明，在体内长时间接触抗原后，TCR触发的Ca(2+) 内流、脱颗粒和细胞毒性在细胞水平上得以维持，而细胞因子产生则因活化诱导的NFAT核转位存在选择性缺陷而严重受损。在慢性感染期间，导致不同效应功能的信号通路的这种差异调节，可能使CD8(+) T细胞通过直接细胞毒性维持一定程度的局部病毒控制，同时通过抑制细胞因子产生来限制全身免疫病理反应。
