TY - JOUR
T1 - Thymus-Derived CD4+CD8+ Cells Reside in Mediastinal Adipose Tissue and the Aortic Arch
AU - Winkels, Holger
AU - Ghosheh, Yanal
AU - Kobiyama, Kouji
AU - Kiosses, William B.
AU - Orecchioni, Marco
AU - Ehinger, Erik
AU - Suryawanshi, Vasantika
AU - Herrera-De La Mata, Sara
AU - Marchovecchio, Paola
AU - Riffelmacher, Thomas
AU - Thiault, Nicolas
AU - Kronenberg, Mitchell
AU - Wolf, Dennis
AU - Seumois, Gregory
AU - Vijayanand, Pandurangan
AU - Ley, Klaus
N1 - Funding Information:
This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Grants HL115232, HL88093, and HL121697 (to K.L.). H.W. was supported by the Deutsche Forschungsgemeinschaft (GZ WI 4811/1-1 and 397484323) and a Tullie and Rickey Families SPARK Award for Innovations in Immunology. The FACSAria II Cell Sorter, the Zeiss LSM 880, and Illumina HiSeq2500 were acquired through National Institutes of Health Office of Research Infrastructure Program Shared Instrumentation Grant Programs S10 RR027366, S10 OD021831, and S10 OD16262.
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Double-positive CD4+CD8ab+ (DP) cells are thought to reside as T cell progenitors exclusively within the thymus. We recently discovered an unexpected CD4+ and CD8ab+ 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.
AB - Double-positive CD4+CD8ab+ (DP) cells are thought to reside as T cell progenitors exclusively within the thymus. We recently discovered an unexpected CD4+ and CD8ab+ 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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U2 - 10.4049/jimmunol.2100208
DO - 10.4049/jimmunol.2100208
M3 - Article
C2 - 34740961
AN - SCOPUS:85122111476
SN - 0022-1767
VL - 207
SP - 2720
EP - 2732
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -