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Publication : Thymus-Derived CD4(+)CD8(+) Cells Reside in Mediastinal Adipose Tissue and the Aortic Arch.

First Author  Winkels H Year  2021
Journal  J Immunol Volume  207
Issue  11 Pages  2720-2732
PubMed ID  34740961 Mgi Jnum  J:337378
Mgi Id  MGI:6849871 Doi  10.4049/jimmunol.2100208
Citation  Winkels H, et al. (2021) Thymus-Derived CD4(+)CD8(+) Cells Reside in Mediastinal Adipose Tissue and the Aortic Arch. J Immunol 207(11):2720-2732
abstractText  Double-positive CD4(+)CD8alphabeta(+) (DP) cells are thought to reside as T cell progenitors exclusively within the thymus. We recently discovered an unexpected CD4(+) and CD8alphabeta(+) immune cell population in healthy and atherosclerotic mice by single-cell RNA sequencing. Transcriptomically, these cells resembled thymic DPs. Flow cytometry and three-dimensional whole-mount imaging confirmed DPs in thymus, mediastinal adipose tissue, and aortic adventitia, but nowhere else. Deep transcriptional profiling revealed differences between DP cells isolated from the three locations. All DPs were dependent on RAG2 expression and the presence of the thymus. Mediastinal adipose tissue DPs resided in close vicinity to invariant NKT cells, which they could activate in vitro. Thymus transplantation failed to reconstitute extrathymic DPs, and frequencies of extrathymic DPs were unaltered by pharmacologic inhibition of S1P1, suggesting that their migration may be locally confined. Our results define two new, transcriptionally distinct subsets of extrathymic DPs that may play a role in aortic vascular homeostasis.
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