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

Autor: Zou D; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.; Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Yin Z; Systems Medicine and Bioengineering Department, Houston Methodist Neal Cancer Center, Houston, TX, USA.; Department of Radiology, Houston Methodist Hospital, Weill Cornell Medicine, Houston, TX, USA., Yi SG; Department of Surgery, J. C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, TX, USA.; Department of Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA., Wang G; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Guo Y; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Xiao X; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Li S; Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA., Zhang X; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Gonzalez NM; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Minze LJ; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA., Wang L; Systems Medicine and Bioengineering Department, Houston Methodist Neal Cancer Center, Houston, TX, USA., Wong STC; Systems Medicine and Bioengineering Department, Houston Methodist Neal Cancer Center, Houston, TX, USA.; Department of Radiology, Houston Methodist Hospital, Weill Cornell Medicine, Houston, TX, USA., Osama Gaber A; Department of Surgery, J. C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, TX, USA.; Department of Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA., Ghobrial RM; Department of Surgery, J. C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, TX, USA.; Department of Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA., Li XC; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.; Department of Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA., Chen W; Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA. wchen@houstonmethodist.org.; Department of Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA. wchen@houstonmethodist.org.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Jan; Vol. 25 (1), pp. 66-76. Date of Electronic Publication: 2024 Jan 02.
DOI: 10.1038/s41590-023-01682-z
Abstrakt: CD4 + T cells are central to various immune responses, but the molecular programs that drive and maintain CD4 + T cell immunity are not entirely clear. Here we identify a stem-like program that governs the CD4 + T cell response in transplantation models. Single-cell-transcriptomic analysis revealed that naive alloantigen-specific CD4 + T cells develop into TCF1 hi effector precursor (T EP ) cells and TCF1 - CXCR6 + effectors in transplant recipients. The TCF1 - CXCR6 + CD4 + effectors lose proliferation capacity and do not reject allografts upon adoptive transfer into secondary hosts. By contrast, the TCF1 hi CD4 + T EP cells have dual features of self-renewal and effector differentiation potential, and allograft rejection depends on continuous replenishment of TCF1 - CXCR6 + effectors from TCF1 hi CD4 + T EP cells. Mechanistically, TCF1 sustains the CD4 + T EP cell population, whereas the transcription factor IRF4 and the glycolytic enzyme LDHA govern the effector differentiation potential of CD4 + T EP cells. Deletion of IRF4 or LDHA in T cells induces transplant acceptance. These findings unravel a stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4 + T EP cells and have implications for T cell-related immunotherapies.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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