Clonal Bifurcation of Foxp3 Expression Visualized in Thymocytes and T Cells

Regulatory T cells (Tregs) are crucial for suppressing autoimmunity and inflammation mediated by conventional T cells. To be useful, some Tregs should have overlapping specificity with relevant self-reactive or pathogen-specific clones. Whether matching recognition between Tregs and non-Tregs might arise through stochastic or deterministic mechanisms has not been addressed. We tested the hypothesis that some Tregs that arise in the thymus or that are induced during Ag-driven expansion of conventional CD4+ T cells might be clonally related to non-Tregs by virtue of asymmetric Foxp3 induction during cell division. We isolated mouse CD4+ thymocytes dividing in vivo, wherein sibling cells exhibited discordant expression of Foxp3 and CD25. Under in vitro conditions that stimulate induced Tregs from conventional mouse CD4+ T cells, we found a requirement for cell cycle progression to achieve Foxp3 induction. Moreover, a substantial fraction of sibling cell pairs arising from induced Treg stimulation also contained discordant expression of Foxp3. Division-linked yet asymmetric induction of Treg fate offers potential mechanisms to anticipate peripheral self-reactivity during thymic selection as well as produce precise, de novo counterregulation during CD4+ T cell–mediated immune responses.

• Publication year

  2018

• Venue

  ImmunoHorizons

• Publication date

  2018-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/immunohorizons.1700064PMID 29707696PMCID 5922779
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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