| Literature DB >> 30065364 |
Yan Li1,2, Guillemette Masse-Ranson1,2,3, Zacarias Garcia2,4, Timothée Bruel3,5, Ayrin Kök6,7, Helene Strick-Marchand1,2, Gregory Jouvion8, Nicolas Serafini1,2, Ai Ing Lim1,2, Mathilde Dusseaux1,2, Thierry Hieu6,7, Franck Bourgade9, Antoine Toubert10,11, Daniela Finke12,13, Olivier Schwartz3,5, Philippe Bousso2,3,4, Hugo Mouquet3,6,7, James P Di Santo14,15.
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.Entities:
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Year: 2018 PMID： 30065364 DOI： 10.1038/s41592-018-0071-6
Source DB: PubMed Journal: Nat Methods ISSN： 1548-7091 Impact factor: 28.547