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Publication : A human immune system mouse model with robust lymph node development.

First Author  Li Y Year  2018
Journal  Nat Methods Volume  15
Issue  8 Pages  623-630
PubMed ID  30065364 Mgi Jnum  J:327313
Mgi Id  MGI:7329945 Doi  10.1038/s41592-018-0071-6
Citation  Li Y, et al. (2018) A human immune system mouse model with robust lymph node development. Nat Methods 15(8):623-630
abstractText  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.
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