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Monocyte-derived TGF-β shapes memory CD8+ T cells

Cellular & Molecular Immunology volume 22, pages 949–950 (2025)Cite this article

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The Original Article was published on 03 June 2025

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Memory CD8 T cells are crucial components of the host immune response against intracellular pathogens and tumors. While the transcriptional and epigenetic programs underlying memory CD8 T-cell differentiation are well known, the extrinsic cues that dictate the acquisition of memory CD8 T-cell fate are relatively understudied. Sun et al. [1] revealed a previously unappreciated role of CCR2+ monocytes in promoting memory CD8+ T-cell fate via membrane-bound TGF-β.

Following acute infection, naïve antigen-specific CD8 T cells in the spleen and lymph nodes proliferate extensively and differentiate into a diverse mixture of short-lived effector cells as well as more durable memory precursor cells. Short-lived effector cells act rapidly to eliminate infected cells, whereas memory precursor cells differentiate into distinct populations of long-lived memory CD8 T cells. As such, this initial bifurcation in T-cell differentiation achieves both immediate pathogen control and durable protection of the host from future reinfections. The mechanistic basis of this divergent differentiation is an area of active investigation. Research using single-cell transfer and cellular barcoding techniques has revealed considerable diversity in how individual T-cell clones differentiate even those bearing identical T-cell receptors [2, 3]. This diversity is thought to be achieved by the aggregate intensity of antigenic stimulation, costimulation and cytokine signaling. A greater intensity of initial activation signals promotes the generation of effector cells, whereas moderate signaling primes the development of memory cells [4, 5].

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References

  1. Sun L, Zhang C, Jiao A, Su Y, Zhang T, Wang Q, et al. CCR2+ monocytes promote memory CD8+ T-cell differentiation via membrane-bound TGF-β. Cell Mol Immunol. 2025;22:869–88.

  2. Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B, Graf P, et al. Disparate individual fates compose robust CD8+ T-cell immunity. Science. 2013;340:630–5.

    Article  CAS  PubMed  Google Scholar 

  3. Gerlach C, Rohr JC, Perie L, Van Rooij N, Van Heijst JWJJ, Velds A, et al. Heterogeneous differentiation patterns of individual CD8+ T cells. Science. 2013;340:635–9.

    Article  CAS  PubMed  Google Scholar 

  4. Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T-cell differentiation. Nat Rev Immunol. 2012;12:749–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Henning AN, Roychoudhuri R, Restifo NP. Epigenetic control of CD8+ T-cell differentiation. Nat Rev Immunol. 2018;18:340–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Duckworth BC, Lafouresse F, Wimmer VC, Broomfield BJ, Dalit L, Alexandre YO, et al. Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands. Nat Immunol. 2021;22:434–48.

  7. Leal JM, Huang JY, Kohli K, Stoltzfus C, Lyons-Cohen MR, Olin BE, et al. Innate cell microenvironments in lymph nodes shape the generation of T-cell responses during type I inflammation. Sci Immunol. 2021;6:eabb9435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Groom JR, Richmond J, Murooka TT, Sorensen EW, Sung JH, Bankert K, et al. CXCR3 Chemokine receptor‒ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity. 2012;37:1091–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sanjabi S, Mosaheb MM, Flavell RA. Opposing effects of TGF-b and IL-15 cytokines control the number of short-lived effector CD8 + T cells. Immunity. 2009;31:131–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thompson EA, Darrah PA, Foulds KE, Hoffer E, Caffrey-Carr A, Norenstedt S, et al. Monocytes acquire the ability to prime tissue-resident T cells via IL-10-mediated TGF-β release. Cell Rep. 2019;28:1127–35.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA

    Mohammad H. Hasan & Lalit K. Beura

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  1. Mohammad H. Hasan
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  2. Lalit K. Beura
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Correspondence to Lalit K. Beura.

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Hasan, M.H., Beura, L.K. Monocyte-derived TGF-β shapes memory CD8+ T cells. Cell Mol Immunol 22, 949–950 (2025). https://doi.org/10.1038/s41423-025-01317-3

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