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Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts.

Sci Rep. 2017 Aug 08;7(1):7536
Yumie Tokunaga 1 , Masamichi Shirouzu 2 , Ryota Sugahara 2 , Yasutoshi Yoshiura 3 , Ikunari Kiryu 4 , Mitsuru Ototake 4 , Takahiro Nagasawa 2 , Tomonori Somamoto 5 , Miki Nakao 2
Yumie Tokunaga 1 , Masamichi Shirouzu 2 , Ryota Sugahara 2 , Yasutoshi Yoshiura 3 , Ikunari Kiryu 4 , Mitsuru Ototake 4 , Takahiro Nagasawa 2 , Tomonori Somamoto 5 , Miki Nakao 2
+ et al

[No authors listed]

Author information
  • 1 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • 2 Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan.
  • 3 Yashima station, Stock Enhancement and Management Department, National Research Institute of Fisheries and Enhancement of Inland Sea, Japan Fisheries Research and Education Agency, 243 Yashima-higashi, Takamatsu, Kagawa, 761-0111, Japan.
  • 4 National Research Institute of Aquaculture, Fisheries Research Agency, Tamaki, Mie, 519-0423, Japan.
  • 5 Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan. somamoto@agr.kyushu-u.ac.jp.

摘要


rag1 -/- zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 -/- zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 -/- fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 -/- fish possess innate protection equivalent to that of rag1 +/- fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.