Department of Pathology, University of Massachusetts Medical School, 368 Plantation Ave, Worcester, Massachusetts 01655, USA.
Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida 32827, USA.
Cold Spring Harb Perspect Biol. 2021 Nov 1;13(11):a038182. doi: 10.1101/cshperspect.a038182.
We have discovered that the determination of CD4 effector and memory fates after infection is regulated not only by initial signals from antigen and pathogen recognition, but also by a second round of such signals at a checkpoint during the effector response. Signals to effectors determine their subsequent fate, inducing further progression to tissue-restricted follicular helpers, cytotoxic CD4 effectors, and long-lived memory cells. The follicular helpers help the germinal center B-cell responses that give rise to high-affinity long-lived antibody responses and memory B cells that synergize with T-cell memory to provide robust long-lived protection. We postulate that inactivated vaccines do not provide extended signals from antigen and pathogen beyond a few days, and thus elicit ineffective CD4 T- and B-cell effector responses and memory. Defining the mechanisms that underlie effective responses should provide insights necessary to develop vaccine strategies that induce more effective and durable immunity.
我们发现，感染后 CD4 效应器和记忆命运的决定不仅受到抗原和病原体识别的初始信号的调节，还受到效应器反应过程中的检查点处第二轮此类信号的调节。效应器的信号决定了它们随后的命运，诱导进一步向组织受限的滤泡辅助细胞、细胞毒性 CD4 效应器和长寿命记忆细胞进展。滤泡辅助细胞有助于生发中心 B 细胞反应，产生高亲和力的长寿命抗体反应和记忆 B 细胞，与 T 细胞记忆协同提供强大的长寿命保护。我们假设，失活疫苗不会在几天之外提供来自抗原和病原体的延长信号，因此会引发无效的 CD4 T 细胞和 B 细胞效应器反应和记忆。确定有效反应的基础机制应该为开发诱导更有效和更持久免疫的疫苗策略提供必要的见解。
