Failure of effector function of human CD8+ T Cells in NOD/SCID/JAK3⁻/⁻ immunodeficient mice transplanted with human CD34+ hematopoietic stem cells

Humanized mice, which are generated by transplanting human CD34+ hematopoietic stem cells into immunodeficient mice, are expected to be useful for the research on human immune responses. It is reported that antigen-specific T cell responses occur in immunodeficient mice transplanted with both human...

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Bibliographic Details
Published in:PloS one 2010-10, Vol.5 (10), p.e13109
Main Authors: Sato, Yoshinori, Takata, Hiroshi, Kobayashi, Naoki, Nagata, Sayaka, Nakagata, Naomi, Ueno, Takamasa, Takiguchi, Masafumi
Format: Article
Language:English
Subjects:
Alloantigens
Animal tissues
Animals
Antigens, CD34 - immunology
CCR7 protein
CD27 antigen
CD28 antigen
CD34 antigen
CD45RA antigen
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Fetuses
Flow Cytometry
Hematopoietic Stem Cell Transplantation
Human behavior
Humans
Immune response
Immunodeficiency
Immunology
Immunology/Immune Response
Immunology/Leukocyte Development
Immunophenotyping
Interferon
Janus Kinase 3 - genetics
Liver
Lymphocytes
Lymphocytes T
Mice
Mice, Inbred NOD
Mice, SCID
Perforin
Rodents
Stem cell transplantation
Stem cells
Studies
T cell receptors
Thymus
γ-Interferon
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Summary:Humanized mice, which are generated by transplanting human CD34+ hematopoietic stem cells into immunodeficient mice, are expected to be useful for the research on human immune responses. It is reported that antigen-specific T cell responses occur in immunodeficient mice transplanted with both human fetal thymus/liver tissues and CD34+ fetal cells, but it remains unclear whether antigen-specific T cell responses occur in those transplanted with only human CD34+ hematopoietic stem cells (HSCs). Here we investigated the differentiation and function of human CD8+ T cells reconstituted in NOD/SCID/Jak3⁻/⁻ mice transplanted with human CD34+ HSCs (hNOK mice). Multicolor flow cytometric analysis demonstrated that human CD8+ T cells generated from the CD34+ HSCs comprised only 3 subtypes, i.e., CD27(high)CD28+CD45RA+CCR7+, CD27+CD28+CD45RA⁻CCR7+, and CD27+CD28+CD45RA⁻CCR7⁻and had 3 phenotypes for 3 lytic molecules, i.e., perforin(Per)⁻granzymeA(GraA)⁻granzymeB(GraB)⁻, Per⁻GraA+GraB⁻, and Per(low)GraA+GraB+. These CD8+ T cells failed to produce IFN-γ and to proliferate after stimulation with alloantigens. These results indicate that the antigen-specific T cell response cannot be elicited in mice transplanted with only human CD34+ HSCs, because the T cells fail to develop normally in such mice.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0013109