Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice

Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice

Abstract Human delta-like 1 (hDlk1) is known to be able to regulate cell fate decisions during hematopoiesis. Mesenchymal stromal cells (MSCs) are known to exhibit potent immunomodulatory roles in a variety of diseases. Herein, we investigated in vivo functions of hDlk1-hMSCs and hDlk1+hMSCs in T ce...

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Autores principales: Do Hee Kwon, Jae Berm Park, Joo Sang Lee, Sung Joo Kim, Bongkum Choi, Ki-Young Lee
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:4e9bf9b6ce09402bb342a1d188592d372021-12-02T16:49:46ZHuman delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice10.1038/s41598-021-90110-z2045-2322https://doaj.org/article/4e9bf9b6ce09402bb342a1d188592d372021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90110-zhttps://doaj.org/toc/2045-2322Abstract Human delta-like 1 (hDlk1) is known to be able to regulate cell fate decisions during hematopoiesis. Mesenchymal stromal cells (MSCs) are known to exhibit potent immunomodulatory roles in a variety of diseases. Herein, we investigated in vivo functions of hDlk1-hMSCs and hDlk1+hMSCs in T cell development and T cell response to viral infection in humanized NOD/SCID/IL-2Rγnull (NSG) mice. Co-injection of hDlk1-hMSC with hCD34+ cord blood (CB) cells into the liver of NSG mice markedly suppressed the development of human T cells. In contrast, co-injection of hDlk1+hMSC with hCD34+ CB cells into the liver of NSG dramatically promoted the development of human T cells. Human T cells developed in humanized NSG mice represent markedly diverse, functionally active, TCR V $$\upbeta $$ β usages, and the restriction to human MHC molecules. Upon challenge with Epstein-Barr virus (EBV), EBV-specific hCD8+ T cells in humanized NSG mice were effectively mounted with phenotypically activated T cells presented as hCD45+hCD3+hCD8+hCD45RO+hHLA-DR+ T cells, suggesting that antigen-specific T cell response was induced in the humanized NSG mice. Taken together, our data suggest that the hDlk1-expressing MSCs can effectively promote the development of human T cells and immune response to exogenous antigen in humanized NSG mice. Thus, the humanized NSG model might have potential advantages for the development of therapeutics targeting infectious diseases in the future.Do Hee KwonJae Berm ParkJoo Sang LeeSung Joo KimBongkum ChoiKi-Young LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Do Hee Kwon
Jae Berm Park
Joo Sang Lee
Sung Joo Kim
Bongkum Choi
Ki-Young Lee
Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
description Abstract Human delta-like 1 (hDlk1) is known to be able to regulate cell fate decisions during hematopoiesis. Mesenchymal stromal cells (MSCs) are known to exhibit potent immunomodulatory roles in a variety of diseases. Herein, we investigated in vivo functions of hDlk1-hMSCs and hDlk1+hMSCs in T cell development and T cell response to viral infection in humanized NOD/SCID/IL-2Rγnull (NSG) mice. Co-injection of hDlk1-hMSC with hCD34+ cord blood (CB) cells into the liver of NSG mice markedly suppressed the development of human T cells. In contrast, co-injection of hDlk1+hMSC with hCD34+ CB cells into the liver of NSG dramatically promoted the development of human T cells. Human T cells developed in humanized NSG mice represent markedly diverse, functionally active, TCR V $$\upbeta $$ β usages, and the restriction to human MHC molecules. Upon challenge with Epstein-Barr virus (EBV), EBV-specific hCD8+ T cells in humanized NSG mice were effectively mounted with phenotypically activated T cells presented as hCD45+hCD3+hCD8+hCD45RO+hHLA-DR+ T cells, suggesting that antigen-specific T cell response was induced in the humanized NSG mice. Taken together, our data suggest that the hDlk1-expressing MSCs can effectively promote the development of human T cells and immune response to exogenous antigen in humanized NSG mice. Thus, the humanized NSG model might have potential advantages for the development of therapeutics targeting infectious diseases in the future.
format article
author Do Hee Kwon
Jae Berm Park
Joo Sang Lee
Sung Joo Kim
Bongkum Choi
Ki-Young Lee
author_facet Do Hee Kwon
Jae Berm Park
Joo Sang Lee
Sung Joo Kim
Bongkum Choi
Ki-Young Lee
author_sort Do Hee Kwon
title Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
title_short Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
title_full Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
title_fullStr Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
title_full_unstemmed Human delta like 1-expressing human mesenchymal stromal cells promote human T cell development and antigen-specific response in humanized NOD/SCID/IL-2R $$\upgamma $$ γ null (NSG) mice
title_sort human delta like 1-expressing human mesenchymal stromal cells promote human t cell development and antigen-specific response in humanized nod/scid/il-2r $$\upgamma $$ γ null (nsg) mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/4e9bf9b6ce09402bb342a1d188592d37
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