A human immune system mouse model with robust lymph node development.
Yan LiGuillemette Masse-RansonZacarias GarciaTimothée BruelAyrin KökHelene Strick-MarchandGregory JouvionNicolas SerafiniAi Ing LimMathilde DusseauxThierry HieuFranck BourgadeAntoine ToubertDaniela FinkeOlivier SchwartzPhilippe BoussoHugo MouquetJames P Di SantoPublished in: Nature methods (2018)
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.
Keyphrases
- lymph node
- endothelial cells
- mouse model
- immune response
- high fat diet induced
- induced apoptosis
- induced pluripotent stem cells
- cell cycle arrest
- squamous cell carcinoma
- hepatitis c virus
- human immunodeficiency virus
- metabolic syndrome
- adipose tissue
- high resolution
- hiv infected
- wild type
- cell death
- skeletal muscle
- bone marrow
- cell proliferation
- high throughput
- hiv aids
- acute respiratory distress syndrome
- hiv testing
- binding protein