Immunology-Oncology Unit, Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, H1T 2M4, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, H3T 1J4, Canada.
Immunol Cell Biol. 2019 Nov;97(10):931-940. doi: 10.1111/imcb.12287. Epub 2019 Sep 18.
Individual CD4 T cells can become one of a number of helper (Th) lineages with distinct effector functions. However, whether biases in Th potential exist prior to antigen encounter is unknown. Studies have identified cell-intrinsic functional heterogeneity among naïve T cells that can be parsed based on the strength of T-cell receptor (TCR) interactions with self-peptide. Here, using CD5 levels as a surrogate for the strength of these basal TCR signals, we sought to identify pre-existing effector biases in the CD4 T-cell lineage. We show that ex vivo-activated CD5 CD4 T cells produce greater amounts of the Th1 cytokine interferon-gamma (IFNγ) than their CD5 counterparts. In addition, a greater percentage of CD5 effector CD4 T cells produce IFNγ in both polyclonal and monoclonal CD4 T-cell populations after antigen challenge in vivo. These results suggest that differential IFNγ production potential exists among CD4 T cells prior to activation and independent of TCR affinity for foreign antigen.
个体 CD4 T 细胞可以成为具有不同效应功能的多种辅助性（Th）谱系之一。然而，在抗原接触之前，Th 潜能是否存在偏向尚不清楚。研究已经确定了初始 T 细胞中的细胞内在功能异质性，可以基于 T 细胞受体（TCR）与自身肽的相互作用强度进行解析。在这里，我们使用 CD5 水平作为这些基础 TCR 信号强度的替代物，试图在 CD4 T 细胞谱系中鉴定预先存在的效应器偏向。我们发现，体外激活的 CD5+CD4 T 细胞比其 CD5 对应物产生更多的 Th1 细胞因子干扰素-γ（IFNγ）。此外，在体内抗原挑战后，多克隆和单克隆 CD4 T 细胞群体中，更大比例的 CD5 效应 CD4 T 细胞产生 IFNγ。这些结果表明，在激活之前，CD4 T 细胞之间存在差异的 IFNγ 产生潜能，并且与 TCR 对外来抗原的亲和力无关。
