Lang Karl S, Recher Mike, Navarini Alexander A, Harris Nicola L, Löhning Max, Junt Tobias, Probst Hans Christian, Hengartner Hans, Zinkernagel Rolf M
Institute of Experimental Immunology, Zurich, Switzerland.
Eur J Immunol. 2005 Mar;35(3):738-45. doi: 10.1002/eji.200425828.
Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent antigen suppressed IL-7Ralpha expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7Ralpha expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Ralpha expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.
持续性是诸如人类免疫缺陷病毒（HIV）、乙型肝炎病毒、丙型肝炎病毒和淋巴细胞脉络丛脑膜炎病毒（LCMV）等病毒感染的一个标志。就LCMV而言，持续性通常可能与CD8(+) T细胞耗竭有关。我们在此证明，持续性抗原会抑制白细胞介素-7受体α（IL-7Rα）的表达，这与T细胞耗竭以及抗凋亡分子B细胞淋巴瘤-2（Bcl-2）表达降低相关。相比之下，暴露于短期存在的抗原只会暂时抑制IL-7Rα的表达，不会诱导T细胞耗竭，反而会启动T细胞。持续性抗原还会抑制已启动T细胞上的IL-7Rα表达，这与先前稳定的已启动T细胞群体的耗竭相关。这些发现表明抗原的持续时间调节T细胞命运。
