David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Division of Infectious Diseases, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
Immunol Rev. 2018 Jul;284(1):91-105. doi: 10.1111/imr.12662.
CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. We discuss research that has provided insight into the diverse viral epitope specificity of CD4 T cells elicited after infection, how this primary response is modified as CD4 T cells home to the lung, establish memory, and after challenge with a secondary and distinct influenza virus strain. Our studies in human subjects point out the challenges facing vaccine efforts to facilitate responses to novel and avian strains of influenza, as well as strategies that enhance the ability of CD4 T cells to promote protective antibody responses to both seasonal and potentially pandemic strains of influenza.
CD4 T 细胞为流感提供了多种不同的功能来保护免疫，这种复杂性使它们与 B 细胞和 CD8 T 细胞区分开来。尽管人们最熟知的 CD4 T 细胞的功能是为抗体产生提供帮助，但 CD4 T 细胞在保护性免疫的许多方面都很重要。我们的研究表明，病毒抗原特异性是 CD4 T 细胞功能的关键决定因素，这一点既可以通过感染的小鼠模型，也可以通过人类疫苗反应来证明，这一因素的重要性至少部分归因于病毒抗原处理过程中的事件。我们讨论了研究成果，这些成果深入了解了感染后诱导的 CD4 T 细胞的多样化病毒表位特异性，以及 CD4 T 细胞归巢到肺部、建立记忆以及在受到二次和不同的流感病毒株挑战时，这种初始反应是如何被改变的。我们在人类受试者中的研究指出了疫苗工作面临的挑战，这些挑战旨在促进对新型和禽源流感株的反应，以及增强 CD4 T 细胞促进对季节性和潜在大流行流感株的保护性抗体反应的能力。
