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Functional Human CD141+ Dendritic Cells in Human Immune System Mice.

Jordana G A Coelho-Dos-Reis1,2, Ryota Funakoshi1, Jing Huang1

  • 1Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA.

The Journal of Infectious Diseases
|October 25, 2019
PubMed
Summary

A new humanized mouse model (HIS mice) successfully mimics the human immune system, enabling the study of functional human dendritic cells (DCs). This model allows for preclinical assessment of vaccine immunogenicity in vivo.

Keywords:
CD141CD1cadenovirus vaccinehuman dendritic cellshuman immune system mice

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Area of Science:

  • Immunology
  • Transplantation Biology

Background:

  • Developing a humanized mouse model is crucial for studying human immune responses.
  • Functional human dendritic cells (DCs) are key components of adaptive immunity.

Purpose of the Study:

  • To establish a humanized mouse model (HIS mice) that accurately reflects the human immune system.
  • To investigate the presence and function of human DCs in vivo.
  • To enable preclinical evaluation of vaccine immunogenicity.

Main Methods:

  • NOD/SCID/IL2Rgammanull (NSG) mice were engrafted with human hematopoietic stem cells (HSCs).
  • Genes for human cytokines and HLA-A2.1 were introduced using adeno-associated virus serotype 9 (AAV9) vectors.
  • HIS mice were immunized with adenovirus-based vaccines expressing malaria/HIV epitopes.

Main Results:

  • Human myeloid DC subsets (CD141+CD11c+ and CD1c+CD11c+) were found in multiple organs of HIS mice.
  • Human DCs isolated from HIS mice induced proliferation of epitope-specific human CD8+ T cells in vitro.
  • Adenovirus-based vaccine immunization led to CD1c upregulation on human CD141+ DCs.

Conclusions:

  • The established HIS mouse model supports functional human DCs.
  • This model is suitable for preclinical assessment of human vaccine immunogenicity.
  • HIS mice provide a valuable platform for advancing vaccine development.