Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Immunol. 2010 Dec;40(12):3472-7. doi: 10.1002/eji.201040587.
NK cells are rapid IFN-γ responders to Plasmodium falciparum-infected erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia in murine models, yet little is known about their contribution to immune responses following malaria infection in humans. Here, we studied the dynamics of and requirements for in vitro NK responses to PfRBC in malaria-naïve volunteers undergoing a single experimental malaria infection under highly controlled circumstances, and in naturally exposed individuals. NK-specific IFN-γ responses to PfRBC following exposure resembled an immunological recall pattern and were tightly correlated with T-cell responses. However, although PBMC depleted of CD56(+) cells retained 20-55% of their total IFN-γ response to PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining PBMC, including NK cells, to produce IFN-γ. Although NK responses to PfRBC were partially dependent on endogenous IL-2 signaling and could be augmented by exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to rescue NK responses in the absence of T cells. Thus, NK cells make a significant contribution to total IFN-γ production in response to PfRBC as a consequence of their dependency on (memory) T-cell help, with likely positive implications for malaria vaccine development.
自然杀伤 (NK) 细胞是体外对疟原虫感染的红细胞 (PfRBC) 产生 IFN-γ 的快速反应细胞，并且在鼠模型中参与控制早期寄生虫血症，但对于人类感染疟疾后其对免疫反应的贡献知之甚少。在此，我们在高度受控的条件下研究了疟原虫初感志愿者和自然暴露个体中体外对 PfRBC 的 NK 反应的动力学和要求。暴露后对 PfRBC 的 NK 特异性 IFN-γ 反应类似于免疫回忆模式，并且与 T 细胞反应密切相关。然而，尽管耗尽 CD56(+)细胞的 PBMC 保留了对 PfRBC 总 IFN-γ 反应的 20-55%，但耗尽 CD3(+)细胞完全消除了剩余 PBMC（包括 NK 细胞）产生 IFN-γ 的能力。尽管 NK 对 PfRBC 的反应部分依赖于内源性 IL-2 信号，但在整个 PBMC 群体中添加外源性 IL-2 可以增强其反应，但在没有 T 细胞的情况下，这一因素不足以挽救 NK 反应。因此，NK 细胞作为依赖 (记忆) T 细胞辅助的结果，对 PfRBC 产生 IFN-γ 做出了重要贡献，这对疟疾疫苗的开发可能具有积极意义。
