Clonal Bifurcation of Foxp3 Expression Visualized in Thymocytes and T Cells.

Autor:	Yen B; Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.; Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032., Fortson KT; Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, New York, NY 10032., Rothman NJ; Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.; Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032., Arpaia N; Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, New York, NY 10032., Reiner SL; Department of Microbiology and Immunology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.; Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2018 Apr 01; Vol. 2 (4), pp. 119-128. Date of Electronic Publication: 2018 Apr 09.
DOI:	10.4049/immunohorizons.1700064
Abstrakt:	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. Competing Interests: DISCLOSURES The authors have no financial conflicts of interest.
Databáze:	MEDLINE
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