Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Front Cell Infect Microbiol. 2023 Feb 10;12:1084526. doi: 10.3389/fcimb.2022.1084526. eCollection 2022.
Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known.
We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti- vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration.
Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting.
Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti- vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against spp.
调节性 T 细胞（Tregs）已被证明可限制针对致病性真菌 spp 的保护性免疫反应，该真菌是孢子丝菌病的病原体。然而，Tregs 在针对这些真菌的疫苗接种中的具体功能尚不清楚。
我们使用 DEREG 小鼠评估了 Tregs 耗竭对实验性重组抗疫苗免疫原性的影响。在该模型中，只有 Foxp3(+) Tregs 表达 eGFP 和白喉毒素 (DT) 受体，并且通过 DT 给药实现 Tregs 的瞬时耗竭。
Tregs 耗竭增强了特异性 IFNγ+ T 细胞（Th1 淋巴细胞）的频率和第一或第二剂疫苗后的细胞因子产生。然而，在第二剂疫苗时耗竭 Tregs 比在第一剂疫苗时引起更大的特异性 Th1 淋巴细胞刺激。同样，与其他免疫组相比，在加强免疫时 Tregs 耗竭后检测到 rSsEno 抗体的 IgG、IgG1 和 IgG2a 产生量最高。重要的是，Tregs 耗竭后疫苗免疫原性的改善也对实验感染模型中挑战后皮肤和肝脏中真菌负荷的更有效降低产生了影响。有趣的是，在加强免疫时 Tregs 耗竭组的真菌负荷降低最大。
我们的结果表明，Tregs 限制了疫苗诱导的免疫反应，并且它们的瞬时耗竭可以增强抗疫苗的免疫原性。需要进一步的研究来阐明 Tregs 耗竭是否可能是提高针对 spp 疫苗效力的一种方法。
