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Smith MJ, Reichenbach DK, Parker SL, et al. T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. JCI Insight. 2017;2(10)doi: 10.1172/jci.insight.92056.
Smith, M. J., Reichenbach, D. K., Parker, S. L., Riddle, M. J., Mitchell, J., Osum, K. C., Mohtashami, M., Stefanski, H. E., Fife, B. T., Bhandoola, A., Hogquist, K. A., Holländer, G. A., Zúñiga-Pflücker, J. C., Tolar, J., & Blazar, B. R. (2017). T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. JCI insight, 2(10), . https://doi.org/10.1172/jci.insight.92056
Smith, Michelle J, et al. "T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction." JCI insight vol. 2,10 (2017). doi: https://doi.org/10.1172/jci.insight.92056
Smith MJ, Reichenbach DK, Parker SL, Riddle MJ, Mitchell J, Osum KC, Mohtashami M, Stefanski HE, Fife BT, Bhandoola A, Hogquist KA, Holländer GA, Zúñiga-Pflücker JC, Tolar J, Blazar BR. T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. JCI Insight. 2017 May 18;2(10). doi: 10.1172/jci.insight.92056. eCollection 2017 May 18. PMID: 28515359; PMCID: PMC5436538.
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JCI Insight. 2017 May 18;2(10). doi: 10.1172/jci.insight.92056. eCollection 2017 May 18.

T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction.

JCI insight

Michelle J Smith, Dawn K Reichenbach, Sarah L Parker, Megan J Riddle, Jason Mitchell, Kevin C Osum, Mahmood Mohtashami, Heather E Stefanski, Brian T Fife, Avinash Bhandoola, Kristin A Hogquist, Georg A Holländer, Juan Carlos Zúñiga-Pflücker, Jakub Tolar, Bruce R Blazar

Affiliations

  1. Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  2. Center for Immunology, Department of Medicine, and.
  3. Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  4. Sunnybrook Research Institute and Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
  5. T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
  6. Department of Biomedicine, University of Basel, Basel, Switzerland.
  7. Department of Paediatrics and Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.

PMID: 28515359 PMCID: PMC5436538 DOI: 10.1172/jci.insight.92056

Abstract

Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs. Upon thymus egress (day 28), proT TEC effects were lost, suggesting that continued signaling from proTs is required to sustain TEC cycling and cellularity. Thymocytes increased significantly by day 21, followed by a significant improvement in mature T cell numbers in the periphery by day 35. This protective surge was temporary, receding by day 60. Double-negative 2 (DN2) proTs selectively increased thymocyte number, while DN3 proTs preferentially increased TECs and T cells in the spleen that persisted at day 60. These findings highlight the importance of the interaction between proTs and TECs in the proliferation and survival of TECs and that the maturation stage of proTs has unique effects on thymopoiesis and peripheral T cell recovery.

Keywords: Immunology; Transplantation

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