A human immune system mouse model with robust lymph node development - Institut Pasteur Access content directly
Journal Articles Nature Methods Year : 2018

A human immune system mouse model with robust lymph node development

Yan Li
Helene Strick-Marchand
  • Function : Author
  • PersonId : 1019959
Thierry Hieu
Franck Bourgade

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-/-SirpaNOD (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 (TFH) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN TFH 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.
No file

Dates and versions

pasteur-02875578 , version 1 (19-06-2020)

Identifiers

Cite

Yan Li, Guillemette Masse-Ranson, Zacarias Garcia, Timothée Bruel, Ayrin Kök, et al.. A human immune system mouse model with robust lymph node development. Nature Methods, 2018, 15 (8), pp.623-630. ⟨10.1038/s41592-018-0071-6⟩. ⟨pasteur-02875578⟩
67 View
0 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More