Immune Signature of Enhanced Functional Avidity CD8(+) T Cells in vivo Induced by Vaccinia Vectored Vaccine.

Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced in vivo are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8+ T cells with relatively high functional avidity to those from DNA vaccine. Herein, we used functional, immune phenotyping and transcriptomic studies to define the immune signature of these CD8+ T cells with high functional avidity. Antigen-specific CD8+ T cells induced by VACV executed superior in vivo killing activity and displayed a distinct transcriptional profile, whereas no significantly differences were found in composition of memory sub-populations and cytokine poly-functionality. Transcriptional analyses revealed unique features of VACV induced CD8+ T cells in several biological processes, including transport, cell cycle, cell communication and metabolic processes. In summary, we characterize CD8+ T cells of high functional avidity induced in vivo by VACV, which not only improves our understanding of adaptive T cell immunity in VACV vaccination, but also provides clues to modulate functional avidity of CD8+ T cells for T cell based immunotherapy.

T细胞的功能亲和力是清除病毒感染和消除肿瘤的关键决定因素。了解T细胞如何维持功能亲和力对于免疫疗法至关重要。然而，仍然缺乏对体内诱导的具有高功能亲和力的T细胞进行系统表征的研究。此前，我们及其他研究人员发现，痘苗病毒载体疫苗（VACV）诱导的抗原特异性CD8 + T细胞相对于DNA疫苗诱导的细胞具有较高的功能亲和力。在此，我们利用功能、免疫表型和转录组学研究来确定这些具有高功能亲和力的CD8 + T细胞的免疫特征。VACV诱导的抗原特异性CD8 + T细胞在体内具有更强的杀伤活性，并显示出独特的转录谱，而在记忆亚群组成和细胞因子多功能性方面未发现显著差异。转录分析揭示了VACV诱导的CD8 + T细胞在几个生物学过程中的独特特征，包括运输、细胞周期、细胞通讯和代谢过程。总之，我们对VACV在体内诱导的具有高功能亲和力的CD8 + T细胞进行了表征，这不仅增进了我们对VACV疫苗接种中适应性T细胞免疫的理解，还为基于T细胞的免疫疗法中调节CD8 + T细胞的功能亲和力提供了线索。