A human immune system mouse model with robust lymph node development

Yan Li; Guillemette Masse-Ranson; Zacarias Garcia; Timothée Bruel; Ayrin Kök; Helene Strick-Marchand; Gregory Jouvion; Nicolas Serafini; Ai Ing Lim; Mathilde Dusseaux; Thierry Hieu; Franck Bourgade; Antoine Toubert; Daniela Finke; Olivier Schwartz; Philippe Bousso; Hugo Mouquet; James P. Di Santo

doi:10.1038/s41592-018-0071-6

A human immune system mouse model with robust lymph node development

Yan Li, Guillemette Masse-Ranson, Zacarias Garcia, Timothée Bruel, Ayrin Kök, Helene Strick-Marchand, Gregory Jouvion, Nicolas Serafini, Ai Ing Lim, Mathilde Dusseaux, Thierry Hieu, Franck Bourgade, Antoine Toubert, Daniela Finke, Olivier Schwartz, Philippe Bousso, Hugo Mouquet, James P. Di Santo

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76 Scopus citations

Abstract

Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2 ^−/− Il2rg ^−/− Sirpa ^NOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (T _FH ) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN T _FH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.

Original language	English (US)
Pages (from-to)	623-630
Number of pages	8
Journal	Nature Methods
Volume	15
Issue number	8
DOIs	https://doi.org/10.1038/s41592-018-0071-6
State	Published - Aug 1 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Biochemistry
Biotechnology
Cell Biology

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Li, Y., Masse-Ranson, G., Garcia, Z., Bruel, T., Kök, A., Strick-Marchand, H., Jouvion, G., Serafini, N., Lim, A. I., Dusseaux, M., Hieu, T., Bourgade, F., Toubert, A., Finke, D., Schwartz, O., Bousso, P., Mouquet, H., & Di Santo, J. P. (2018). A human immune system mouse model with robust lymph node development. Nature Methods, 15(8), 623-630. https://doi.org/10.1038/s41592-018-0071-6

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title = "A human immune system mouse model with robust lymph node development",

abstract = " Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2 −/− Il2rg −/− Sirpa NOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (T FH ) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN T FH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.",

author = "Yan Li and Guillemette Masse-Ranson and Zacarias Garcia and Timoth{\'e}e Bruel and Ayrin K{\"o}k and Helene Strick-Marchand and Gregory Jouvion and Nicolas Serafini and Lim, {Ai Ing} and Mathilde Dusseaux and Thierry Hieu and Franck Bourgade and Antoine Toubert and Daniela Finke and Olivier Schwartz and Philippe Bousso and Hugo Mouquet and {Di Santo}, {James P.}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = aug,

day = "1",

doi = "10.1038/s41592-018-0071-6",

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Li, Y, Masse-Ranson, G, Garcia, Z, Bruel, T, Kök, A, Strick-Marchand, H, Jouvion, G, Serafini, N, Lim, AI, Dusseaux, M, Hieu, T, Bourgade, F, Toubert, A, Finke, D, Schwartz, O, Bousso, P, Mouquet, H & Di Santo, JP 2018, 'A human immune system mouse model with robust lymph node development', Nature Methods, vol. 15, no. 8, pp. 623-630. https://doi.org/10.1038/s41592-018-0071-6

TY - JOUR

T1 - A human immune system mouse model with robust lymph node development

AU - Li, Yan

AU - Masse-Ranson, Guillemette

AU - Garcia, Zacarias

AU - Bruel, Timothée

AU - Kök, Ayrin

AU - Strick-Marchand, Helene

AU - Jouvion, Gregory

AU - Serafini, Nicolas

AU - Lim, Ai Ing

AU - Dusseaux, Mathilde

AU - Hieu, Thierry

AU - Bourgade, Franck

AU - Toubert, Antoine

AU - Finke, Daniela

AU - Schwartz, Olivier

AU - Bousso, Philippe

AU - Mouquet, Hugo

AU - Di Santo, James P.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2 −/− Il2rg −/− Sirpa NOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (T FH ) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN T FH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.

AB - Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2 −/− Il2rg −/− Sirpa NOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (T FH ) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN T FH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.

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U2 - 10.1038/s41592-018-0071-6

DO - 10.1038/s41592-018-0071-6

M3 - Article

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AN - SCOPUS:85051562745

SN - 1548-7091

VL - 15

SP - 623

EP - 630

JO - Nature Methods

JF - Nature Methods

IS - 8

ER -

A human immune system mouse model with robust lymph node development

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