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International Immunology, Vol. 13, No. 6, 777-783, June 2001
© 2001 Japanese Society for Immunology

Suppression of thymic development by the dominant-negative form of Gads

Kazu Kikuchi1, Yoshitada Kawasaki1, Naoto Ishii1, Yoshiteru Sasaki1, Hironobu Asao1, Toshikazu Takeshita3, Ichiro Miyoshi2, Noriyuki Kasai2 and Kazuo Sugamura1,4

1 Department of Microbiology and Immunology, and
2 The Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
3 Department of Bacteriology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
4 CREST Program of the Japan Science and Technology Corporation, Sendai 980-8575, Japan

Correspondence to: K. Sugamura, Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Gads, a hematopoietic-lineage-specific Grb2 family member, is involved in the signaling mediated by the TCR through its interactions with SLP-76 and LAT. Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter. The total number of thymocytes was profoundly reduced in the transgenic mice, whereas in the double-negative (CD4–CD8–) thymocyte subset, in particular the CD25+CD44– pre-T cell population, it was significantly increased. However, CD5 expression, which is mediated by pre-TCR stimulation, was significantly suppressed on the CD4–CD8– thymocytes of the transgenic mice. Furthermore, the SLP-76-dependent signaling was markedly suppressed as well. These data suggest that Gads plays an important role in the pre-TCR as well as TCR signaling in thymocytes.

Keywords: Grb2 family, LAT, pre-TCR signaling, SLP-76, TCR signaling

Transmitting editor: T. Kurosaki


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