CD4+ T cell immunity is dependent on an intrinsic stem-like program

CD4+ T cell immunity is dependent on an intrinsic stem-like program

2024 January ; 25(1): 66–76. doi:10.1038/s41590-023-01682-z. | Dawei Zou, Zheng Yin, Stephanie G. Yi, Guohua Wang, Yang Guo, Xiang Xiao, Shuang Li, Xiaolong Zhang, Nancy M. Gonzalez, Laurie J. Minze, Lin Wang, Stephen T. C. Wong, A. Osama Gaber, Rafik M. Ghobrial, Xian C. Li, Wenhao Chen
The study identifies a stem-like program that governs CD4+ T cell immunity in transplantation models. Single-cell transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1+CXCR6+ effectors in transplant recipients. TCF1 sustains the CD4+ TEP cell population, while IRF4 and LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells leads to transplant acceptance, as these cells lose their proliferative ability and do not persist. This study highlights the importance of the stem-like program in maintaining CD4+ T cell immunity and provides insights into the regulation of CD4+ T cell responses in transplantation and other immune contexts.The study identifies a stem-like program that governs CD4+ T cell immunity in transplantation models. Single-cell transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1+CXCR6+ effectors in transplant recipients. TCF1 sustains the CD4+ TEP cell population, while IRF4 and LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells leads to transplant acceptance, as these cells lose their proliferative ability and do not persist. This study highlights the importance of the stem-like program in maintaining CD4+ T cell immunity and provides insights into the regulation of CD4+ T cell responses in transplantation and other immune contexts.
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[slides and audio] CD4%5E%2B T cell immunity is dependent on an intrinsic stem-like program