Natural killer cells inhibit the development of autoantibody production in (C57BL/6 x DBA/2) F1 hybrid mice injected with DBA/2 spleen cells.
We investigated the role of natural killer (NK) cells in the development of autoantibody production in which (C57BL/6 x DBA/2) F1 (BDF1) hybrid mice were injected intravenously with spleen cells (SC) from parental DBA/2 mice (treated BDF1 mice). Treated BDF1 mice began to show an increase in serum anti-dsDNA antibody 2 weeks after injection, while the NK activity of their SC transiently increased initially in the first 1 to 2 weeks after injection, but subsequently decreased dramatically. Flow cytometric analysis suggested that this sequential change in NK activity correlated with the absolute number of host-derived NK1.1+ cells in SC from treated BDF1 mice. We demonstrated that the level of anti-dsDNA in serum is directly influenced by the level of NK activity in treated BDF1 mice. Depletion of NK cells by administration of anti-NK1.1 mAb accelerated the development of autoantibody production, whereas augmentation of NK activity by administration of poly-(I:C) inhibited the development of autoantibody production. This inhibitory effect of poly(I:C) was abolished by prior depletion of NK cells. Interestingly, suppression of autoantibody production was seen only when poly(I:C) was administrated within 1 week after injection of parental SC. Last, we demonstrate that adoptive transfer of interleukin-2 (IL-2)-activated NK cells had a protective effect against the development of autoantibody production. These findings imply that NK cells may have a protective role in lupus-like disease especially in its early stage. In addition, it opens up the possibility that adoptive immunotherapy with IL-2-activated NK cells can delay or even prevent the development of autoimmune disease.
Harada
M
M
Department of Immunology, Kyushu University, Fukuoka, Japan.
Lin
T
T
Kurosawa
S
S
Maeda
T
T
Umesue
M
M
Itoh
O
O
Matsuzaki
G
G
Nomoto
K
K
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002678:Chimera; D004195:Disease Models, Animal; D005260:Female; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D001323:Autoantibodies; D007376:Interleukin-2