Interferon regulatory factor 4 controls effector functions of CD8 + memory T cells.

Autor: Harberts A; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schmidt C; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schmid J; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Reimers D; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Koch-Nolte F; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Mittrücker HW; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany h.mittruecker@uke.de f.raczkowski@uke.de., Raczkowski F; Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany h.mittruecker@uke.de f.raczkowski@uke.de.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Apr 20; Vol. 118 (16).
DOI: 10.1073/pnas.2014553118
Abstrakt: The transcription factor IRF4 is required for CD8 + T cell activation, proliferation, and differentiation to effector cells and thus is essential for robust CD8 + T cell responses. The function of IRF4 in memory CD8 + T cells yet needs to be explored. To investigate the role of IRF4 for maintaining differentiation state and survival of CD8 + memory T cells, we used a mouse model with tamoxifen-inducible Irf4 knockout to preclude effects due to inefficient memory cell differentiation in absence of IRF4. We infected mice with ovalbumin-recombinant listeria and induced Irf4 knockout after clearance of the pathogen. Loss of IRF4 resulted in phenotypical changes of CD8 + memory T cells but did not cause a reduction of the total memory T cell population. However, upon reencounter of the pathogen, CD8 + memory T cells showed impaired expansion and acquisition of effector functions. When compared to CD8 + effector memory T cells, CD8 + tissue-resident memory T cells (T RM cells) expressed higher IRF4 levels. Mice with constitutive Irf4 knockout had diminished CD8 + T RM -cell populations, and tamoxifen-induced Irf4 deletion caused a reduction of this cell population. In conclusion, our results demonstrate that IRF4 is required for effective reactivation but not for general survival of CD8 + memory T cells. Formation and maintenance of CD8 + T RM cells, in contrast, appear to depend on IRF4.
Competing Interests: The authors declare no competing interest.
Databáze: MEDLINE
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