Bim regulates the survival and suppressive capability of CD8+ FOXP3+ regulatory T cells during murine GVHD.

Blood
Kimberle AgleWilliam R Drobyski

Abstract

CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft-versus-host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppression of GVHD. To define the mechanistic basis for this observation, we examined the T-cell repertoire and the transcriptional profile of in vivo-derived CD4+ and CD8+ Tregs that emerged early during this disease. Polyclonal and alloantigen-induced CD8+ Tregs had repertoire diversity that was similar to that of conventional CD8+ T cells, indicating that a restricted repertoire was not the proximate cause of decreased suppression. Transcriptional profiling revealed that CD8+ Tregs possessed a canonical Treg transcriptional signature that was similar to that observed in CD4+ Tregs, yet distinct from conventional CD8+ T cells. Pathway analysis, however, demonstrated that CD8+ Tregs had differential gene expression in pathways involved in cell death and survival. This was further confirmed by detailed mRNA sequence analysis and protein expression studies, which demonstrated that CD8+ Tregs had increased expression of Bim ...Continue Reading

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Citations

Sep 23, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Supinya IamsawatXue-Zhong Yu
Aug 17, 2019·British Journal of Haematology·Shlomo Elias, Alexander Y Rudensky
Apr 3, 2019·Frontiers in Immunology·Kripa GuramAndrew B Sharabi
Mar 25, 2019·Frontiers in Immunology·Govindarajan Thangavelu, Bruce R Blazar
May 16, 2019·Leukemia·Tamara J BlätteLars Bullinger
Jan 28, 2021·European Journal of Immunology·Veronika NiederlovaOndrej Stepanek

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