Nideffer Jason, Bach Florian, Nankya Felistas, Musinguzi Kenneth, Borna Šimon, Mantilla Michelle, Zedi Maato, Garcia Romero Aracely, Gerungan Chloe, Yang Nora, Kim Soyeon, van der Ploeg Kattria, Camanag Kylie, Lopez Luis, Nansubuga Evelyn, Nankabirwa Joaniter I, Arinaitwe Emmanuel, Boonrat Potchara, Strubbe Steven, Cepika Alma-Martina, Takahashi Saki, Dorsey Grant, Greenhouse Bryan, Rodriguez-Barraquer Isabel, Kamya Moses R, Bacchetta Rosa, Ssewanyana Isaac, Haque Ashraful, Roncarolo Maria Grazia, Jagannathan Prasanna
Department of Medicine, Stanford University, Stanford, CA, USA.
Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Sci Immunol. 2025 Apr 25;10(106):eads2957. doi: 10.1126/sciimmunol.ads2957.
Few studies have tracked human CD4 T cell clones through repeated infections. We used longitudinal single-cell RNA and T cell receptor (TCR) tracking to study the functional stability and memory potential of CD4 T cell clonotypes during repeated () infections in Ugandan children and adults. Nearly all clonotypes displayed a strong preference for one of seven CD4 subsets. This phenomenon of "clonal fidelity" was influenced by clonal expansion, linking T cell polarization and proliferation in vivo. Using clone tracking, we characterized subset-specific activation trajectories and identified antigen-specific clones. Type 1 regulatory T (T1) cells accounted for nearly 90% of -specific CD4 T cells in blood. Tracking these clones longitudinally for hundreds of days, we observed malaria-induced expansion of T1 effectors, long-term persistence of T1 memory cells, and high-fidelity recall responses after reinfection. This work establishes clonal fidelity as a natural phenomenon and demonstrates the stable, long-term memory potential of T1 cells.
很少有研究通过反复感染来追踪人类CD4 T细胞克隆。我们利用纵向单细胞RNA和T细胞受体（TCR）追踪技术，研究了乌干达儿童和成人在反复（）感染期间CD4 T细胞克隆型的功能稳定性和记忆潜能。几乎所有克隆型都对七个CD4亚群之一表现出强烈偏好。这种“克隆保真度”现象受克隆扩增影响，将体内T细胞极化与增殖联系起来。通过克隆追踪，我们表征了亚群特异性激活轨迹并鉴定了抗原特异性克隆。1型调节性T（T1）细胞占血液中特异性CD4 T细胞的近90%。对这些克隆进行长达数百天的纵向追踪，我们观察到疟疾诱导的T1效应细胞扩增、T1记忆细胞的长期持续存在以及再次感染后的高保真回忆反应。这项工作将克隆保真度确立为一种自然现象，并证明了T1细胞具有稳定的长期记忆潜能。
