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

Research output: Contribution to journalArticlepeer-review

72 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 languageEnglish (US)
Pages (from-to)623-630
Number of pages8
JournalNature Methods
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Biotechnology
  • Cell Biology

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