Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice
Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice
复制标题
DOI：
10.1172/jci58762
复制
发表时间：
2012-03-01
影响因子：
15.9
通讯作者：
Klein, Bruce
中科院分区：
文献类型：
--
作者：
Nanjappa, Som G.;Heninger, Erika;Klein, Bruce
免疫功能低下的个体，包括CD4（+）T细胞较少的艾滋病患者，机会性真菌感染的风险增加。这种感染的发病率在世界范围内不断增加，这意味着对抗真菌疫苗的需求正在增加。虽然CD4（+）T细胞在抵抗许多病原性真菌感染中起主导作用，但我们先前已经表明，在缺乏CD4（+）T细胞的情况下，疫苗接种可以诱导保护性抗真菌CD8（+）T细胞免疫。然而，还没有确定疫苗诱导的抗真菌CD8（+）T细胞记忆是否可以在没有CD4（+）T细胞帮助的情况下维持。在这里，我们已经在芽生菌病疫苗接种的小鼠模型中表明，抗真菌记忆CD8（+）T细胞在没有CD4（+）T细胞的情况下维持至少6个月而不丧失数量或功能，并且细胞保护免受感染。使用一个系统，使我们能够诱导和跟踪抗原特异性，抗真菌的CD8（+）T细胞，我们发现，这样的细胞在转移到幼稚小鼠缺乏CD4（+）T细胞和持久性真菌抗原后，至少维持5个月。此外，真菌疫苗接种诱导了与CD8（+）T细胞中持久记忆功能相关的转录因子谱。因此，与细菌和病毒不同，真菌引起长期的CD8（+）T细胞记忆，而无需CD4（+）T细胞帮助或持久性抗原。这对开发免疫功能低下患者有效的新型抗真菌疫苗策略具有重要意义。
Individuals who are immunocompromised, including AIDS patients with few CD4(+) T cells, are at increased risk for opportunistic fungal infections. The incidence of such infections is increasing worldwide, meaning that the need for antifungal vaccines is increasing. Although CD4(+) T cells play a dominant role in resistance to many pathogenic fungal infections, we have previously shown that vaccination can induce protective antifungal CD8(+) T cell immunity in the absence of CD4(+) T cells. However, it has not been determined whether vaccine-induced antifungal CD8(+) T cell memory can be maintained in the absence of CD4(+) T cell help. Here, we have shown in a mouse model of vaccination against blastomycosis that antifungal memory CD8(+) T cells are maintained in the absence of CD4(+) T cells without loss of numbers or function for at least 6 months and that the cells protect against infection. Using a system that enabled us to induce and track antigen-specific, antifungal CD8(+) T cells, we found that such cells were maintained for at least 5 months upon transfer into naive mice lacking both CD4(+) T cells and persistent fungal antigen. Additionally, fungal vaccination induced a profile of transcription factors functionally linked with persistent memory in CD8(+) T cells. Thus, unlike bacteria and viruses, fungi elicit long-term CD8(+) T cell memory that is maintained without CD4(+) T cell help or persistent antigen. This has implications for the development of novel antifungal vaccine strategies effective in immunocompromised patients.