Acute viral infection generates lineage-committed Th1 and T follicular helper (Tfh) memory cells that recall their lineage-specific functions following secondary challenge with virus. However, the lineage commitment of effector and memory Th cells in vivo following protein vaccination is poorly understood. In this study, we analyzed effector and memory CD4⁺ T cell differentiation in mice (Mus musculus) following adjuvanted glycoprotein immunization compared with acute lymphocytic choriomeningitis virus infection. Glycoprotein immunization induced CXCR5⁻ non-Tfh effector and memory CD4⁺ T cells that surprisingly had not undergone polarization toward any particular Th cell lineage but had undergone memory differentiation. However, upon challenge with virus, these Th lineage–nonpolarized memory CD4⁺ T cells were able to generate Th1 secondary effector cells, demonstrating their lineage plasticity. In addition, Tfh and memory Tfh cells were generated in response to protein immunization, and these cells differed from infection-induced Tfh cells by their lack of the transcription factor Tbet. Rechallenge experiments demonstrated that viral infection, but not protein immunization, during either the primary or secondary immune response, restricts the recall of Bcl6 expression and the generation of germinal center Tfh cells. Together, these data demonstrate that protein immunization generates a combination of nonpolarized memory cells that are highly plastic and memory Tfh cells that can undergo further Th1-like modulation during a secondary response to viral infection.

急性病毒感染会产生谱系确定的 Th1 和 T 滤泡辅助 (Tfh) 记忆细胞，这些细胞在病毒的二次攻击后回忆其谱系特异性功能。然而，人们对蛋白质疫苗接种后体内效应和记忆Th细胞的谱系承诺知之甚少。在这项研究中，我们分析了与急性淋巴细胞性脉络丛脑膜炎病毒感染相比，辅助糖蛋白免疫后小鼠（小家鼠）的效应和记忆 CD4 ^{+ T 细胞分化。}糖蛋白免疫诱导 CXCR5 ^-非 Tfh 效应子和记忆 CD4 ⁺T 细胞出人意料地没有经历向任何特定 Th 细胞谱系的极化，而是经历了记忆分化。然而，在病毒攻击后，这些 Th 谱系非极化记忆 CD4 ⁺T 细胞能够产生 Th1 次级效应细胞，证明了它们的谱系可塑性。此外，Tfh 和记忆 Tfh 细胞是响应蛋白质免疫产生的，这些细胞与感染诱导的 Tfh 细胞不同，因为它们缺乏转录因子 Tbet。再攻击实验表明，在初级或次级免疫反应期间，病毒感染而不是蛋白质免疫，限制了 Bcl6 表达的回忆和生发中心 Tfh 细胞的产生。总之，这些数据表明，蛋白质免疫产生了高度可塑性的非极化记忆细胞和记忆 Tfh 细胞的组合，这些细胞可以在对病毒感染的二次反应期间进行进一步的 Th1 样调节。