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Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, w...

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Autores principales: Talaie, Tara, Wang, Hui, Kuo, Wan-I, Danzl, Nichole, Gulsen, Mert R., Wolabaugh, Amber N., Ding, Xiaolan, Sykes, Megan, Li, Hao Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213218/
https://www.ncbi.nlm.nih.gov/pubmed/37251390
http://dx.doi.org/10.3389/fimmu.2023.1159341
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author Talaie, Tara
Wang, Hui
Kuo, Wan-I
Danzl, Nichole
Gulsen, Mert R.
Wolabaugh, Amber N.
Ding, Xiaolan
Sykes, Megan
Li, Hao Wei
author_facet Talaie, Tara
Wang, Hui
Kuo, Wan-I
Danzl, Nichole
Gulsen, Mert R.
Wolabaugh, Amber N.
Ding, Xiaolan
Sykes, Megan
Li, Hao Wei
author_sort Talaie, Tara
collection PubMed
description Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.
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spelling pubmed-102132182023-05-27 Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue Talaie, Tara Wang, Hui Kuo, Wan-I Danzl, Nichole Gulsen, Mert R. Wolabaugh, Amber N. Ding, Xiaolan Sykes, Megan Li, Hao Wei Front Immunol Immunology Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation. Frontiers Media S.A. 2023-05-12 /pmc/articles/PMC10213218/ /pubmed/37251390 http://dx.doi.org/10.3389/fimmu.2023.1159341 Text en Copyright © 2023 Talaie, Wang, Kuo, Danzl, Gulsen, Wolabaugh, Ding, Sykes and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Talaie, Tara
Wang, Hui
Kuo, Wan-I
Danzl, Nichole
Gulsen, Mert R.
Wolabaugh, Amber N.
Ding, Xiaolan
Sykes, Megan
Li, Hao Wei
Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title_full Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title_fullStr Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title_full_unstemmed Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title_short Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
title_sort origin, phenotype and autoimmune potential of t cells in human immune system mice receiving neonatal human thymus tissue
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213218/
https://www.ncbi.nlm.nih.gov/pubmed/37251390
http://dx.doi.org/10.3389/fimmu.2023.1159341
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