Immunology-Oncology Unit, Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
Eur J Immunol. 2021 Jun;51(6):1365-1376. doi: 10.1002/eji.202048788. Epub 2021 Mar 19.
Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4 T cells. Further, we describe a relationship between CD5 levels on naïve human CD4 T cells and binding affinity to foreign peptide, in addition to a predominance of CD5 T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5 and CD5 naïve human CD4 T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4 T cells with important implications for the identification of functionally biased T- cell populations that can be exploited to improve the efficacy of adoptive cell therapies.
研究表明，在鼠模型中，T 细胞受体（TCR）与自身肽的亚阈值相互作用对于胸腺发育和初始 T 细胞在外周的存活是必需的。最近，通过细胞表面 CD5 水平读出的，TCR 与自身肽的紧张性相互作用的强度差异与小鼠中分选的 T 细胞群体之间的不同效应潜力相关。然而，CD5 是否也可用于解析人类 T 细胞中的功能异质性尚不清楚。我们的研究表明，CD5 水平与人类初始 CD4 T 细胞中的 TCR 信号强度相关。此外，我们描述了初始人 CD4 T 细胞上 CD5 水平与对外来肽的结合亲和力之间的关系，以及 CD5 T 细胞在记忆区室中的优势。CD5 和 CD5 初始人 CD4 T 细胞之间的基因表达差异和细胞因子产生潜力的偏向性与在小鼠中的观察结果一致。总之，这些数据验证了使用 CD5 表面水平作为人类初始 CD4 T 细胞异质性的标志物的合理性，这对于鉴定功能偏向的 T 细胞群体具有重要意义，这些群体可用于提高过继细胞疗法的疗效。
