Trivedi Shubhanshi, Cheng Olivia J, Brintz Ben J, Charles Richelle C, Leung Daniel T
Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84132, United States.
Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84108, United States.
Oxf Open Immunol. 2025 Mar 25;6(1):iqaf002. doi: 10.1093/oxfimm/iqaf002. eCollection 2025.
Mucosal-associated invariant T (MAIT) cells are unconventional innate-like T cells abundant in human mucosal tissues and are associated with protective responses to microbial infections. MAIT cells have the capacity for rapid effector functions, including the secretion of cytokines and cytotoxic molecules. In this study, we examined the longitudinal circulating MAIT cell response to the live attenuated oral vaccine Ty21a (Ty21a) against serovar Typhi (. Typhi). We enrolled healthy adults who received a course of oral live-attenuated Typhi strain Ty21a vaccine and assessed peripheral blood MAIT cell longitudinal responses pre-vaccination, and at seven days and one-month post-vaccination, using flow cytometry, cell migration, and tetramer decay assays. We showed that following vaccination, circulating MAIT cells were lower in frequency, but were more activated, and had higher levels of gut-homing marker integrin α4β7 and chemokine receptors CCR9 and CCR6, suggesting the potential of MAIT cells to migrate to mucosal sites. We found no significant differences in MAIT cell functionality, cytotoxicity and T-cell receptor avidity, except in TNF expression, which was higher post-vaccination. We show that MAIT cell immune responses are modulated post-vaccination against Typhi. This study contributes to our understanding of MAIT cells' potential role in oral vaccination against bacterial mucosal pathogens.
黏膜相关恒定T（MAIT）细胞是一种非传统的固有样T细胞，在人类黏膜组织中大量存在，并且与针对微生物感染的保护性反应相关。MAIT细胞具有快速发挥效应功能的能力，包括分泌细胞因子和细胞毒性分子。在本研究中，我们检测了针对伤寒杆菌（Typhi）血清型的减毒活口服疫苗Ty21a（Ty21a）引起的循环MAIT细胞的纵向反应。我们招募了接受口服减毒伤寒杆菌Ty21a疫苗疗程的健康成年人，并使用流式细胞术、细胞迁移和四聚体衰变分析，评估了接种疫苗前、接种后7天和1个月时外周血MAIT细胞的纵向反应。我们发现，接种疫苗后，循环MAIT细胞的频率降低，但激活程度更高，并且肠道归巢标志物整合素α4β7以及趋化因子受体CCR9和CCR6的水平更高，这表明MAIT细胞有迁移至黏膜部位的潜力。我们发现，除了接种疫苗后肿瘤坏死因子（TNF）表达较高外，MAIT细胞的功能、细胞毒性和T细胞受体亲和力没有显著差异。我们表明，接种疫苗后MAIT细胞的免疫反应针对伤寒杆菌受到了调节。本研究有助于我们理解MAIT细胞在针对细菌性黏膜病原体的口服疫苗接种中的潜在作用。
