Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP3R1), failed to demonstrate increased [Ca2+]i or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP3R1 expression, but expressed the type-2 and -3 receptors, IP3R2 and IP3R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007–6011, and Jayaraman and Marks (1997) Mol. Cell. Biol. 17, 3005–3012]. The authors concluded that IP3R1 is essential for TCR signalling and suggested that Ca2+ release via IP3R1 is a critical mediator of apoptosis. To establish whether a loss of IP3R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP3R1-deficient (IP3R1-/-) mice. As IP3R1-/- mice die at weaning, we transplanted bone marrow cells of IP3R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP3R1-containing (IP3R1+/+) lymphocytes were replaced by the donor IP3R1-/- lymphocytes after transplantation and that expression of IP3R2 and IP3R3 was unaltered. In contrast with the previous reports, T-cells lacking IP3R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP3R1+/+ and IP3R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP3R1 is not essential for T-cell development and function.
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August 1998
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Research Article|
August 01 1998
T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling?
Junji HIROTA;
*Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), c/o Banyu Pharmaceutical Co., Ltd. 2-9-3 Shimomeguro, Meguro-ku, Tokyo 153, Japan
†Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
2To whom correspondence should be addressed, at the Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo (e-mail:jhirota@ims.u-tokyo.ac.jp).
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Masashi BABA;
Masashi BABA
1
‡Department of Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
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Mineo MATSUMOTO;
Mineo MATSUMOTO
†Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
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Teiichi FURUICHI;
Teiichi FURUICHI
†Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
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Kiyoshi TAKATSU;
Kiyoshi TAKATSU
‡Department of Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
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Katsuhiko MIKOSHIBA
Katsuhiko MIKOSHIBA
*Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), c/o Banyu Pharmaceutical Co., Ltd. 2-9-3 Shimomeguro, Meguro-ku, Tokyo 153, Japan
†Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
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Publisher: Portland Press Ltd
Received:
March 10 1998
Revision Received:
April 24 1998
Accepted:
May 13 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 333 (3): 615–619.
Article history
Received:
March 10 1998
Revision Received:
April 24 1998
Accepted:
May 13 1998
Citation
Junji HIROTA, Masashi BABA, Mineo MATSUMOTO, Teiichi FURUICHI, Kiyoshi TAKATSU, Katsuhiko MIKOSHIBA; T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling?. Biochem J 1 August 1998; 333 (3): 615–619. doi: https://doi.org/10.1042/bj3330615
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