PMID- 31647546 OWN - NLM STAT- MEDLINE DCOM- 20201001 LR - 20211204 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 221 IP - 2 DP - 2020 Jan 2 TI - Functional Human CD141+ Dendritic Cells in Human Immune System Mice. PG - 201-213 LID - 10.1093/infdis/jiz432 [doi] AB - BACKGROUND: For the purpose of studying functional human dendritic cells (DCs) in a humanized mouse model that mimics the human immune system (HIS), a model referred to as HIS mice was established. METHODS: Human immune system mice were made by engrafting NOD/SCID/IL2Rgammanull (NSG) mice with human hematopoietic stem cells (HSCs) following the transduction of genes encoding human cytokines and human leukocyte antigen (HLA)-A2.1 by adeno-associated virus serotype 9 (AAV9) vectors. RESULTS: Our results indicate that human DC subsets, such as CD141+CD11c+ and CD1c+CD11c+ myeloid DCs, distribute throughout several organs in HIS mice including blood, bone marrow, spleen, and draining lymph nodes. The CD141+CD11c+ and CD1c+CD11c+ human DCs isolated from HIS mice immunized with adenoviruses expressing malaria/human immunodeficiency virus (HIV) epitopes were able to induce the proliferation of malaria/HIV epitopes-specific human CD8+ T cells in vitro. Upregulation of CD1c was also observed in human CD141+ DCs 1 day after immunization with the adenovirus-based vaccines. CONCLUSIONS: Establishment of such a humanized mouse model that mounts functional human DCs enables preclinical assessment of the immunogenicity of human vaccines in vivo. CI - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. FAU - Coelho-Dos-Reis, Jordana G A AU - Coelho-Dos-Reis JGA AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. AD - Department of Microbiology, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. FAU - Funakoshi, Ryota AU - Funakoshi R AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. FAU - Huang, Jing AU - Huang J AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. FAU - Pereira, Felipe Valenca AU - Pereira FV AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. AD - Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Iketani, Sho AU - Iketani S AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. AD - Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Tsuji, Moriya AU - Tsuji M AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Adenovirus Vaccines) RN - 0 (Antigens, Surface) RN - 0 (THBD protein, human) RN - 0 (Thrombomodulin) SB - IM MH - Adenovirus Vaccines/*immunology MH - Animals MH - Antigens, Surface/*immunology MH - Dendritic Cells/*immunology MH - Disease Models, Animal MH - Humans MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Thrombomodulin PMC - PMC7457331 OTO - NOTNLM OT - CD141 OT - CD1c OT - adenovirus vaccine OT - human dendritic cells OT - human immune system mice EDAT- 2019/10/28 06:00 MHDA- 2020/10/02 06:00 PMCR- 2021/01/02 CRDT- 2019/10/25 06:00 PHST- 2018/12/12 00:00 [received] PHST- 2019/08/20 00:00 [accepted] PHST- 2019/10/28 06:00 [pubmed] PHST- 2020/10/02 06:00 [medline] PHST- 2019/10/25 06:00 [entrez] PHST- 2021/01/02 00:00 [pmc-release] AID - 5606696 [pii] AID - jiz432 [pii] AID - 10.1093/infdis/jiz432 [doi] PST - ppublish SO - J Infect Dis. 2020 Jan 2;221(2):201-213. doi: 10.1093/infdis/jiz432.