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Foreign antigen-independent memory-phenotype CD4+ T cells: a new player in innate immunity?

Nature Reviews Immunology volume 18, page 1 (2018)Cite this article

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In an Opinion article published in May 2017 (Antigen-inexperienced memory CD8+ T cells: where they come from and why we need them. Nat. Rev. Immunol. 17, 391–400 (2017)1), Ross Kedl and colleagues provided a comprehensive review concerning foreign antigen-inexperienced CD8+ T lymphocytes with a memory phenotype (MP). This population develops without foreign antigen recognition and consists of thymus-derived innate memory (TIM) and peripherally generated virtual memory (TVM) cells. Importantly, these CD8+ MP lymphocyte subsets exert innate effector function in terms of cytokine production2 and/or host resistance to infection in vivo3.

From available evidence, these authors argued that CD4+ T cells fail to generate a corresponding foreign antigen-independent MP population in lymphoreplete mice while likely doing so in humans1. They based this hypothesis in part on the observations that most murine CD44hi CD4+ T cells are CD49d+ (a marker for antigen-specific effector and/or memory CD8+ T cells)4, and that CD44hi CD4+ T cells are virtually absent in T cell receptor (TCR)-transgenic Rag-deficient mice in steady state5.

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References

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Acknowledgements

The authors are grateful to R. N. Germain and the late W. E. Paul for their invaluable discussions and contributions to the work on this topic. T.K., J.Z. and A.S. are funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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  1. Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA

    Takeshi Kawabe & Alan Sher

  2. Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA

    Jinfang Zhu

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  1. Takeshi Kawabe
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Correspondence to Takeshi Kawabe or Alan Sher.

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Kawabe, T., Zhu, J. & Sher, A. Foreign antigen-independent memory-phenotype CD4+ T cells: a new player in innate immunity?. Nat Rev Immunol 18, 1 (2018). https://doi.org/10.1038/nri.2018.12

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