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EMBO Rep. 2017 Jun;18(6):885-893. doi: 10.15252/embr.201643321. Epub 2017 May 2.

Hyper-reactive cloned mice generated by direct nuclear transfer of antigen-specific CD4+ T cells.

Author information

1
Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan osamuk@yamanashi.ac.jp ogura@rtc.riken.go.jp.
2
Bioresource Center RIKEN, Tsukuba, Japan.
3
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan.
4
Center for Life Science Research, University of Yamanashi, Chuo, Japan.
5
Drug Discovery & Disease Research Laboratory, SHIONOGI & Co., Ltd., Osaka, Japan.
6
Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
7
Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Japan.
8
Bioresource Center RIKEN, Tsukuba, Japan osamuk@yamanashi.ac.jp ogura@rtc.riken.go.jp.

Abstract

T-cell receptor (TCR)-transgenic mice have been employed for evaluating antigen-response mechanisms, but their non-endogenous TCR might induce immune response differently than the physiologically expressed TCR Nuclear transfer cloning produces animals that retain the donor genotype in all tissues including germline and immune systems. Taking advantage of this feature, we generated cloned mice that carry endogenously rearranged TCR genes from antigen-specific CD4+ T cells. We show that T cells of the cloned mice display distinct developmental pattern and antigen reactivity because of their endogenously pre-rearranged TCRα (rTα) and TCRβ (rTβ) alleles. These alleles were transmitted to the offspring, allowing us to establish a set of mouse lines that show chronic-type allergic phenotypes, that is, bronchial and nasal inflammation, upon local administrations of the corresponding antigens. Intriguingly, the existence of either rTα or rTβ is sufficient to induce in vivo hypersensitivity. These cloned mice expressing intrinsic promoter-regulated antigen-specific TCR are a unique animal model with allergic predisposition for investigating CD4+ T-cell-mediated pathogenesis and cellular commitment in immune diseases.

KEYWORDS:

CD4+ T cell; T‐cell receptor; allergy; somatic cell nuclear transfer

PMID:
28468955
PMCID:
PMC5452041
DOI:
10.15252/embr.201643321
[Indexed for MEDLINE]
Free PMC Article

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