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Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates

Beth C. Holbrook and Martha A. Alexander-Miller
J Immunol September 2, 2020, ji2000461; DOI: https://doi.org/10.4049/jimmunol.2000461
Beth C. Holbrook
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101
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Martha A. Alexander-Miller
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101
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Key Points

  • Foxp3+ cells are more highly represented in newborn spleen, lung, and circulation.

  • Newborn Tregs express higher levels of Foxp3 and CD25 compared with adults.

  • Newborn and adult Tregs differ in their survival and response to TCR engagement.

Abstract

T regulatory cells (Tregs) play a critical role in controlling the immune response, often limiting pathogen-specific cells to curb immune-mediated damage. Studies in human infants have reported an increased representation of Tregs in these individuals. However, how these cells differ from those in adults at various sites and how they respond to activation signals is relatively unknown. In this study, we used a newborn nonhuman primate model to assess Treg populations present at multiple sites with regard to frequency and phenotype in comparison with those present in adult animals. We found that Foxp3+ cells were more highly represented in the T cell compartment of newborn nonhuman primates for all sites examined (i.e., the spleen, lung, and circulation). In the spleen and circulation, newborn-derived Tregs expressed significantly higher levels of Foxp3 and CD25 compared with adults, consistent with an effector phenotype. Strikingly, the phenotype of Tregs in the lungs of adult and infant animals was relatively similar, with both adult and newborn Tregs exhibiting a more uniform PD-1+CD39+ phenotype. Finally, in vitro, newborn Tregs exhibited an increased requirement for TCR engagement for survival. Further, these cells upregulated CD39 more robustly than their adult counterpart. Together, these data provide new insights into the quantity of Tregs in newborns, their activation state, and their potential to respond to activation signals.

Footnotes

  • This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) Grant R01AI098339 (to M.A.A.-M.). The Vervet Research Colony is supported in part by NIH Grant P40 OD010965 (to Matthew Jorgensen, principal investigator). Services were provided by the Cell and Viral Vector Core, the Synthetic Chemistry Core, and the Flow Cytometry Core Laboratories of the Wake Forest Comprehensive Cancer Center, supported in part by National Cancer Institute Grant P30 CA121291.

  • The online version of this article contains supplemental material.

  • Received April 28, 2020.
  • Accepted August 4, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.

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The Journal of Immunology: 206 (2)
The Journal of Immunology
Vol. 206, Issue 2
15 Jan 2021
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Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates
Beth C. Holbrook, Martha A. Alexander-Miller
The Journal of Immunology September 2, 2020, ji2000461; DOI: 10.4049/jimmunol.2000461

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Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates
Beth C. Holbrook, Martha A. Alexander-Miller
The Journal of Immunology September 2, 2020, ji2000461; DOI: 10.4049/jimmunol.2000461
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Print ISSN 0022-1767        Online ISSN 1550-6606