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2005: Shimizu Ichiro; Tomita Yukihiro; Iwai Toshiro; Zhang Qi-Wei; Matsuzaki Goro; Nomoto Kikuo; Yasui Hisataka
The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the recognition and rejection of the alloantigen in vivo.
Transplant international : official journal of the European Society for Organ Transplantation 2005;18(9):1090-9.
Ly-49A is an inhibitory receptor that binds H-2Dd and H-2Dk. The downregulation of Ly-49A is thought to mediate NK self tolerance in vivo. In this study, we analyzed the regulation of Ly-49A, D and G2 on NK cells in an in vivo rejection model. After injection with 1 x 10(8) B10.D2 spleen cells (SC) into B 10 mice, we found Ly-49A downregulated within 3 h on NK cells of B10 mice, whereas expressions of Ly-49D and G2 were augmented. To investigate effects of different expression patterns of Ly-49 receptors on NK cells, Ly-49A, D or G2-depleted B10 mice were inoculated with B10.D2 SC. NK cells from SC of Ly-49A-depleted and B10.D2 SC-injected B10 mice showed enhanced cytotoxicity to Dd-positive targets in vitro. Furthermore, reduced numbers of B10.D2 SC were observed in Ly-49A or G2-depleted B10 mice, whereas increased numbers of B10.D2 SC were observed in Ly-49D-depleted B10 mice after inoculation with B10.D2 SC in vivo. These findings indicated that the downregulation of Ly-49A and the augmentation of Ly-49D expression may mediate NK cells to recognize and kill Dd antigen efficiently. In conclusion, each Ly-49 isoform may play independent roles in the regulation of activation or inhibition on NK cells.

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