CD4⁺ T helper (Th) cells are fundamental players in immunity. Based on the expression of signature cytokines and transcription factors, several Th subsets have been defined. Th cells are thought to be far more heterogeneous and multifunctional than originally believed, but characterization of the full diversity has been hindered by technical limitations. Here, we employ mass cytometry to analyze the diversity of Th cell responses generated in vitro and in animal disease models, revealing a vast heterogeneity of effector states with distinct cytokine footprints. The diversities of cytokine responses established during primary antigen encounters in Th1- and Th2-cell-polarizing conditions are largely maintained after secondary challenge, regardless of the new inflammatory environment, highlighting many of the identified states as stable Th cell sublineages. We also find that Th17 cells tend to upregulate Th2-cell-associated cytokines upon challenge, indicating a closer developmental connection between Th17 and Th2 cells than previously anticipated.

CD4 ⁺ T 辅助 (Th) 细胞是免疫的基本参与者。基于标志性细胞因子和转录因子的表达，已经定义了几个 Th 亚群。人们认为 Th 细胞的异质性和多功能性比原先认为的要多得多，但完全多样性的表征受到技术限制的阻碍。在这里，我们采用质谱流式细胞术来分析体外产生的 Th 细胞反应的多样性在动物疾病模型中，揭示了具有不同细胞因子足迹的效应子状态的巨大异质性。无论新的炎症环境如何，在 Th1 和 Th2 细胞极化条件下初级抗原相遇期间建立的细胞因子反应的多样性在二级攻击后很大程度上保持不变，突出了许多已鉴定的状态为稳定的 Th 细胞亚系。我们还发现 Th17 细胞在受到攻击时倾向于上调 Th2 细胞相关细胞因子，表明 Th17 和 Th2 细胞之间的发育联系比以前预期的更紧密。