Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Briefing
  • Published:

Reversing T cell immunity reveals the basis for T cell lineage fate determination

Switching the CD4 and CD8 coreceptor proteins encoded in Cd4 and Cd8 loci results in a reversed T cell immune system, with CD4+ cytotoxic T cells and CD8+ helper T cells. Thus, whichever coreceptor is encoded in Cd4 promotes a helper lineage fate, and whichever is encoded in Cd8 promotes a cytotoxic lineage fate.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Switching of coreceptor proteins encoded by the Cd4 and Cd8 loci in FlipFlop mice.

References

  1. Taniuchi, I. CD4 Helper and CD8 Cytotoxic T Cell Differentiation. Annu. Rev. Immunol. 36, 579–601 (2018). This review summarizes the transcription factor network that regulates T cell lineage fate.

    Article  CAS  Google Scholar 

  2. Itano, A. et al. The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells. J. Exp. Med. 183, 731–741 (1996). This study proposes that coreceptor signaling strength dictates the helper versus cytotoxic lineage fate.

    Article  CAS  Google Scholar 

  3. Karimi, M. M. et al. The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat. Commun. 12, 99 (2021). This study uses single-cell RNA sequencing of thymocytes to conclude that signaling strength is the basis of T cell lineage determination.

    Article  CAS  Google Scholar 

  4. Singer, A., Adoro, S. & Park, J. H. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat. Rev. Immunol. 8, 788–801 (2008). This review discusses different perspectives of lineage fate determination in the thymus.

    Article  CAS  Google Scholar 

  5. Brugnera, E. et al. Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells. Immunity 13, 59–71 (2000). This study proposes the kinetic signaling model.

    Article  CAS  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Shinzawa, M. et al. Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus. Nat. Immunol. https://doi.org/10.1038//s41590-022-01187-1 (2022).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reversing T cell immunity reveals the basis for T cell lineage fate determination. Nat Immunol 23, 656–657 (2022). https://doi.org/10.1038/s41590-022-01195-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-022-01195-1

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing