Department of Immunology and Genomic Medicine, National Jewish Health, Denver, Colorado, United States of America.
Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, United States of America.
PLoS Pathog. 2021 Jun 9;17(6):e1009602. doi: 10.1371/journal.ppat.1009602. eCollection 2021 Jun.
The CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4+ T cell response. While the most prevalent clones and clonotypes exhibited some tissue selectivity, most were observed to reside in both the lung and lung-draining lymph nodes. Antigen-reactivity of the broader repertoires was predicted to be shared across both tissues and individual mice. Transcriptome, trajectory, and chromatin accessibility analysis of lung and lymph-node repertoires revealed three unique but related populations of responding IL-4+ CD4+ T cells consistent with T follicular helper, T helper 2, and a transitional population sharing similarity with both populations. The shared antigen reactivity of lymph node and lung repertoires combined with the adoption of tissue-specific gene programs allows for the pairing of cellular and humoral responses critical to the orchestration of anti-helminth immunity.
CD4+T 细胞反应对于宿主抵御寄生虫感染至关重要。宿主和组织之间的这种反应如何变化，仍然是我们理解中的一个重要空白。利用 IL-4 报告小鼠来鉴定对巴西旋毛虫感染的反应性 CD4+T 细胞，T 细胞受体测序与新的聚类算法相结合，揭示了广泛反应性和克隆多样性的 CD4+T 细胞反应。虽然最常见的克隆和克隆型表现出一定的组织选择性，但大多数观察到存在于肺和肺引流淋巴结中。更广泛的反应谱的抗原反应性预计在两个组织和个体小鼠中是共享的。肺和淋巴结反应谱的转录组、轨迹和染色质可及性分析揭示了三种独特但相关的反应性 IL-4+CD4+T 细胞群体，与滤泡辅助 T 细胞、辅助性 T 细胞 2 和一种过渡性群体一致，它们与两种群体都有相似之处。淋巴结和肺反应谱的共享抗原反应性以及组织特异性基因程序的采用，允许对细胞和体液反应进行配对，这对于寄生虫免疫的协调至关重要。
