Razvi E S, Jiang Z, Woda B A, Welsh R M
Department of Pathology, University of Massachusetts Medical Center, Worcester 10655-0125, USA.
Am J Pathol. 1995 Jul;147(1):79-91.
This report examines the mechanisms involved in the down-regulation of the immune response in acute viral infection and documents the presence of apoptotic lymphocytes in situ in the spleens of mice during the resolution of the immune response to acute lymphocytic choriomeningitis virus infection. Apoptotic cells were detected by an in situ nucleotidyl transferase assay. Both T and B lymphocytes were shown to be dying in vivo, the latter in clusters. A biphasic occurrence of apoptosis during the course of the acute infection was observed, with elevated levels occurring at day 3 after infection and a second more pronounced peak at day 11 after infection, coincident with the decline of the cytotoxic T lymphocyte response and with the decrease in total splenic leukocyte number. Apoptosis in vivo was detected in lpr mice, suggesting that Fas expression is not imperative for lymphocyte apoptosis in the context of an acute viral infection. Apoptosis in situ and the decline of the T lymphocyte response to acute lymphocytic choriomeningitis virus infection was unaffected by the enforced lymphocyte-directed expression of Bcl-2, a protein that blocks growth factor deprivation-induced apoptosis of lymphocytes in vitro. These results argue that the silencing of the T cell response to acute infection may not be a result simply of growth factor deprivation. The susceptibility of activated T cells to apoptotic death, which has previously been associated with virus-induced immune deficiency, may therefore also explain the en masse elimination of the expanded lymphocyte pool subsequent to an acute viral infection.
本报告研究了急性病毒感染中免疫反应下调所涉及的机制，并记录了在小鼠脾脏中，急性淋巴细胞性脉络丛脑膜炎病毒感染免疫反应消退过程中原位凋亡淋巴细胞的存在情况。通过原位核苷酸转移酶测定法检测凋亡细胞。结果显示，T淋巴细胞和B淋巴细胞均在体内发生死亡，后者呈簇状死亡。在急性感染过程中观察到凋亡呈双相性发生，在感染后第3天凋亡水平升高，在感染后第11天出现第二个更明显的峰值，这与细胞毒性T淋巴细胞反应的下降以及脾脏白细胞总数的减少相一致。在lpr小鼠体内检测到凋亡，这表明在急性病毒感染的情况下，Fas表达对于淋巴细胞凋亡并非必不可少。原位凋亡以及T淋巴细胞对急性淋巴细胞性脉络丛脑膜炎病毒感染反应的下降不受Bcl-2强制淋巴细胞定向表达的影响，Bcl-2是一种在体外可阻断生长因子剥夺诱导的淋巴细胞凋亡的蛋白质。这些结果表明，T细胞对急性感染反应的沉默可能不仅仅是生长因子剥夺的结果。活化T细胞对凋亡死亡的易感性，此前已与病毒诱导的免疫缺陷相关，因此也可能解释了急性病毒感染后大量扩增的淋巴细胞池被清除的现象。
