The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the recognition and rejection of the alloantigen in vivo.
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.
Shimizu
Ichiro
I
Department of Cardiovascular Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tomita
Yukihiro
Y
Iwai
Toshiro
T
Zhang
Qi-Wei
QW
Matsuzaki
Goro
G
Nomoto
Kikuo
K
Yasui
Hisataka
H
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000032:analysis / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020033:Protein Isoforms; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens; D037181:Lectins, C-Type; D020033:Protein Isoforms; D055630:Receptors, NK Cell Lectin-Like