Steffen Teresa, Ajendra Jesuthas, Koschel Marianne, Palmen Alexander, Wegner Hannah, Risch Frederic, Bach Luisa, Ritter Manuel, Hübner Marc P, Baumjohann Dirk
Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, University of Bonn, Bonn, Germany.
Eur J Immunol. 2025 May;55(5):e202451400. doi: 10.1002/eji.202451400.
T follicular helper (T) cells are the primary CD4 T helper cell subset providing help to B cells for efficient antibody responses in vaccination, allergy, autoimmunity, and infectious diseases. Despite their critical involvement in immunity, T cells' specific role in filarial infections remains unclear. Using the rodent filarial model Litomosoides sigmodontis, we examined T and germinal center (GC) B cell responses in lung-draining mediastinal lymph nodes (medLNs) over a 110-day infection period in naive and infected wildtype (WT) BALB/c mice, as well as eosinophil-deficient dblGATA mice, using flow cytometry and ELISA. We observed robust and prolonged T and GC B cell responses in medLNs of infected BALB/c mice, along with enduring IgG1 antibody responses next to a persistent systemic humoral immune response. We further provide evidence of dysregulated T/T follicular regulatory (T) cell ratios in medLNs. Finally, elevated T cell frequencies in medLNs of dblGATA mice reaffirm the significant role of eosinophils during chronic infection. In conclusion, our findings provide novel insights into population changes of T and GC B cells during filarial infection.
滤泡辅助性T（TFH）细胞是主要的CD4辅助性T细胞亚群，在疫苗接种、过敏、自身免疫和传染病中为B细胞提供帮助，以实现有效的抗体反应。尽管TFH细胞在免疫中起着关键作用，但其在丝虫感染中的具体作用仍不清楚。我们使用啮齿动物丝虫模型Sigmodontis，通过流式细胞术和酶联免疫吸附测定（ELISA），在110天的感染期内，检测了未感染和已感染的野生型（WT）BALB/c小鼠以及嗜酸性粒细胞缺陷的dblGATA小鼠肺引流纵隔淋巴结（medLN）中的TFH和生发中心（GC）B细胞反应。我们观察到，在感染的BALB/c小鼠的medLN中，TFH和GC B细胞反应强烈且持续时间长，同时伴随着持久的全身体液免疫反应，IgG1抗体反应也持续存在。我们进一步提供了medLN中TFH/滤泡调节性T（TFR）细胞比例失调的证据。最后，dblGATA小鼠medLN中TFH细胞频率升高，再次证实了嗜酸性粒细胞在慢性感染中的重要作用。总之，我们的研究结果为丝虫感染期间TFH和GC B细胞的群体变化提供了新的见解。
