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A human immune system mouse model with robust lymph node development
- Source :
- Nature Methods, Nature Methods, Nature Publishing Group, 2018, 15 (8), pp.623-630. ⟨10.1038/s41592-018-0071-6⟩, Nature Methods, 2018, 15 (8), pp.623-630. ⟨10.1038/s41592-018-0071-6⟩
- Publication Year :
- 2017
-
Abstract
- International audience; 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.
- Subjects :
- 0301 basic medicine
Male
T-Lymphocytes
MESH: Lymph Nodes
HIV Infections
Biochemistry
MESH: Mice, Knockout
MESH: HIV-1
Mice
MESH: Animals
Lymph node
Mice, Knockout
MESH: Cytokines
B-Lymphocytes
Mice, Inbred BALB C
MESH: Virus Latency
MESH: HIV Infections
3. Good health
Virus Latency
medicine.anatomical_structure
Lymphatic system
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
MESH: Immunoglobulin Class Switching
Cytokines
Female
Lymph
Biotechnology
Interleukin Receptor Common gamma Subunit
MESH: Mice, Transgenic
Transgene
MESH: Mice, Inbred BALB C
Mice, Transgenic
Biology
MESH: Models, Immunological
03 medical and health sciences
Immune system
Thymic Stromal Lymphopoietin
Immunity
MESH: Mice, Inbred C57BL
MESH: B-Lymphocytes
medicine
Animals
Humans
Secondary lymphoid tissue
Molecular Biology
MESH: Mice
MESH: Humans
MESH: Interleukin Receptor Common gamma Subunit
Models, Immunological
Cell Biology
Immunoglobulin Class Switching
MESH: Male
Mice, Inbred C57BL
030104 developmental biology
MESH: T-Lymphocytes
Immunoglobulin class switching
Immunology
HIV-1
Lymph Nodes
MESH: Female
Subjects
Details
- ISSN :
- 15487105 and 15487091
- Volume :
- 15
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature methods
- Accession number :
- edsair.doi.dedup.....152ed891295814431a971358f8be482b