A human immune system mouse model with robust lymph node development

Nat Methods. 2018 Aug;15(8):623-630. doi: 10.1038/s41592-018-0071-6. Epub 2018 Jul 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • HIV Infections / immunology
  • HIV-1
  • Humans
  • Immunoglobulin Class Switching
  • Interleukin Receptor Common gamma Subunit / deficiency
  • Interleukin Receptor Common gamma Subunit / genetics
  • Lymph Nodes / cytology
  • Lymph Nodes / growth & development*
  • Lymph Nodes / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Virus Latency / immunology

Substances

  • Cytokines
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • thymic stromal lymphopoietin