Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY.
Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY.
Immunohorizons. 2023 Oct 1;7(10):696-707. doi: 10.4049/immunohorizons.2300081.
The amphibian Xenopus laevis tadpole provides a unique comparative experimental organism for investigating the roles of innate-like T (iT) cells in tolerogenic immunity during early development. Unlike mammals and adult frogs, where conventional T cells are dominant, tadpoles rely mostly on several prominent distinct subsets of iT cells interacting with cognate nonpolymorphic MHC class I-like molecules. In the present study, to investigate whole T cell responsiveness ontogenesis in X. laevis, we determined in tadpoles and adult frogs the capacity of splenic T cells to proliferate in vivo upon infection with two different pathogens, ranavirus FV3 and Mycobacterium marinum, as well as in vitro upon PHA stimulation using the thymidine analogous 5-ethynyl-2'-deoxyuridine and flow cytometry. We also analyzed by RT-quantitative PCR T cell responsiveness upon PHA stimulation. In vivo tadpole splenic T cells showed limited capacity to proliferate, whereas the in vitro proliferation rate was higher than adult T cells. Gene markers for T cell activation and immediate-early genes induced upon TCR activation were upregulated with similar kinetics in tadpole and adult splenocytes. However, the tadpole T cell signature included a lower amplitude in the TCR signaling, which is a hallmark of mammalian memory-like T cells and iT or "preset" T cells. This study suggests that reminiscent of mammalian neonatal T cells, tadpole T cells are functionally different from their adult counterpart.
非洲爪蟾（Xenopus laevis）蝌蚪为研究固有样 T（iT）细胞在早期发育过程中耐受免疫中的作用提供了一种独特的比较实验生物。与哺乳动物和成年青蛙不同，常规 T 细胞占主导地位，蝌蚪主要依赖于几种明显不同的 iT 细胞亚群，与同源非多态 MHC 类 I 样分子相互作用。在本研究中，为了研究非洲爪蟾 X. laevis 中整个 T 细胞反应的发生，我们在蝌蚪和成年青蛙中确定了脾 T 细胞在感染两种不同病原体（Ranavirus FV3 和 Mycobacterium marinum）后的体内增殖能力，以及在 PHA 刺激下用胸苷类似物 5-乙炔基-2'-脱氧尿苷和流式细胞术在体外的增殖能力。我们还通过 RT-定量 PCR 分析了 PHA 刺激后的 T 细胞反应。体内蝌蚪脾 T 细胞增殖能力有限，而体外增殖率高于成年 T 细胞。T 细胞激活的基因标记物和 TCR 激活后诱导的即刻早期基因以相似的动力学在蝌蚪和成年脾细胞中上调。然而，蝌蚪 T 细胞的特征包括 TCR 信号转导的幅度较低，这是哺乳动物记忆样 T 细胞和 iT 或“预设”T 细胞的标志。这项研究表明，类似于哺乳动物新生儿 T 细胞，蝌蚪 T 细胞在功能上与成年 T 细胞不同。
