Van Fossen Dana M, Cho Hyunjae, Wagar Lisa E, Ma Jennie Z, Parsonnet Julie, Haque Rashidul, Davis Mark M, Petri William A
Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, USA.
mBio. 2025 Apr 9;16(4):e0398024. doi: 10.1128/mbio.03980-24. Epub 2025 Mar 10.
T follicular helper (Tfh) cells are crucial for B cell activation and subsequent antibody production. This functionality is influenced by surface markers such as CD40L, a costimulatory factor which promotes B cell activation, and CD57, which is a well-known marker of senescence. This study examined age-specific differences in Tfh cell function in Bangladeshi and American children. At age two, Bangladeshi children displayed impaired CD40L upregulation and significant CD57 downregulation upon stimulation. These patterns, not observed in American children of the same age, suggested an exhaustion-like phenotype potentially driven by environmental factors. Random forest and generalized estimating equations (GEE) modeling was used to analyze predictors of Tfh cell response to stimulation. Days since the last antibiotic treatment, total antibiotic treatments, diarrheal episodes, and malnutrition were identified as variables that significantly impacted the Tfh response to stimuli. To assess Tfh cell ability to promote antibody responses, we correlated Tfh functionality with antibody concentration post-vaccination and in response to infection with , an endemic apicomplexan parasite. Increased CD40L expression upon stimulation correlated positively with anti-Poliovirus type 2/3 neutralizing antibody and anti-Cp17 (a sporozoite antigen) IgA concentrations. In contrast, increased CD57 expression was significantly correlated with decreased anti-Cp17 IgA. This indicates that an activation-supportive phenotype (CD40L+) may be more effective in promoting immunity than a senescent phenotype (CD57+). Together, these findings suggest that early-life environmental exposures may program Tfh cell functionality, impacting immune response potential in settings with high pathogen exposure.
T follicular helper (Tfh) cells are upstream mediators that shape the humoral immune response to specific antigens. The generation of an effective memory response to infection is vital to prevent subsequent reinfections. However, in areas with high burdens of exposure to infections, such as the urban community from Bangladesh studied here, children are consistently exposed to inflammatory pathogens. Specific environmental exposures significantly influenced Tfh cell activation and senescence phenotypes. Additionally, Tfh cell responses correlated with antibody concentrations following vaccination or infection, indicating that environmental factors may play a critical role in shaping effective immunity in early childhood.
滤泡辅助性T（Tfh）细胞对于B细胞活化及随后的抗体产生至关重要。这种功能受表面标志物影响，如促进B细胞活化的共刺激因子CD40L，以及作为衰老知名标志物的CD57。本研究调查了孟加拉国和美国儿童Tfh细胞功能的年龄特异性差异。在两岁时，孟加拉国儿童在受到刺激后CD40L上调受损且CD57显著下调。这些模式在同龄美国儿童中未观察到，提示可能由环境因素驱动的类似耗竭的表型。使用随机森林和广义估计方程（GEE）模型分析Tfh细胞对刺激反应的预测因素。自上次抗生素治疗后的天数、抗生素治疗总次数、腹泻发作次数和营养不良被确定为显著影响Tfh对刺激反应的变量。为评估Tfh细胞促进抗体反应的能力，我们将Tfh功能与接种疫苗后及感染（一种地方性顶复门寄生虫）后的抗体浓度相关联。刺激后CD40L表达增加与抗2型/3型脊髓灰质炎病毒中和抗体及抗Cp17（一种子孢子抗原）IgA浓度呈正相关。相反，CD57表达增加与抗Cp17 IgA降低显著相关。这表明激活支持性表型（CD40L +）在促进免疫方面可能比衰老表型（CD57 +）更有效。总之，这些发现表明早期生活中的环境暴露可能编程Tfh细胞功能，影响高病原体暴露环境中的免疫反应潜力。
滤泡辅助性T（Tfh）细胞是塑造针对特定抗原的体液免疫反应的上游介质。对感染产生有效的记忆反应对于预防后续再感染至关重要。然而，在感染暴露负担高的地区，如此处研究的孟加拉国城市社区，儿童持续暴露于炎性病原体。特定的环境暴露显著影响Tfh细胞活化和衰老表型。此外，Tfh细胞反应与接种疫苗或感染后的抗体浓度相关，表明环境因素可能在塑造幼儿期有效免疫方面起关键作用。
