Viramontes Karla M, Thone Melissa N, DeRogatis Julia M, Neubert Emily N, Henriquez Monique L, De La Torre Jamie-Jean, Tinoco Roberto
Center for Virus Research, Chao Family Comprehensive Cancer Center, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA, United States.
Immunohorizons. 2025 Jan 23;9(1). doi: 10.1093/immhor/vlae002.
The differentiation and functionality of virus-specific T cells during acute viral infections are crucial for establishing long-term protective immunity. While numerous molecular regulators impacting T cell responses have been uncovered, the role of cellular prion proteins (PrPc) remains underexplored. Here, we investigated the impact of PrPc deficiency on the differentiation and function of virus-specific T cells using the lymphocytic choriomeningitis virus (LCMV) Armstrong acute infection model. Our findings reveal that Prnp-/- mice exhibit a robust expansion of virus-specific CD8+ T cells, with similar activation profiles as wild-type mice during the early stages of infection. However, Prnp-/- mice had higher frequencies and numbers of virus-specific memory CD8+ T cells, along with altered differentiation profiles characterized by increased central and effector memory subsets. Despite similar proliferation rates early during infection, Prnp-/- memory CD8+ T cells had decreased proliferation compared with their wild-type counterparts. Additionally, Prnp-/- mice had higher numbers of cytokine-producing memory CD8+ T cells, indicating a more robust functional response. Furthermore, Prnp-/- mice had increased virus-specific CD4+ T cell responses, suggesting a broader impact of PrPc deficiency on T cell immunity. These results unveil a previously unrecognized role for PrPc in regulating the differentiation, proliferation, and functionality of virus-specific T cells, providing valuable insights into immune system regulation by prion proteins during viral infections.
急性病毒感染期间病毒特异性T细胞的分化和功能对于建立长期保护性免疫至关重要。虽然已经发现了许多影响T细胞反应的分子调节因子，但细胞朊蛋白（PrPc）的作用仍未得到充分研究。在这里，我们使用淋巴细胞性脉络丛脑膜炎病毒（LCMV）阿姆斯特朗急性感染模型研究了PrPc缺陷对病毒特异性T细胞分化和功能的影响。我们的研究结果表明，Prnp-/-小鼠表现出病毒特异性CD8+T细胞的强劲扩增，在感染早期其激活谱与野生型小鼠相似。然而，Prnp-/-小鼠具有更高频率和数量 的病毒特异性记忆CD8+T细胞，以及以中央和效应记忆亚群增加为特征的改变的分化谱。尽管在感染早期增殖率相似，但Prnp-/-记忆CD8+T细胞与野生型对应细胞相比增殖减少。此外，Prnp-/-小鼠产生细胞因子的记忆CD8+T细胞数量更多，表明其功能反应更强。此外，Prnp-/-小鼠的病毒特异性CD4+T细胞反应增加，表明PrPc缺陷对T细胞免疫有更广泛的影响。这些结果揭示了PrPc在调节病毒特异性T细胞的分化、增殖和功能方面以前未被认识的作用，为病毒感染期间朊蛋白对免疫系统的调节提供了有价值的见解。
