Ly-49D transfected NK cells show reduced interleukin-10 production in response to H-2d and increased lytic activity: implication by interaction using class I MHC alloantigen+ target cells in pregnancy.
OBJECTIVE
Mating of CBA/J (H-2k) with DBA/2 (H-2d) males leads to a high rate of spontaneous resorption (about 40%), which is not seen in other mating combinations, such as CBA/J X BALB/c. The activation of natural killer cells (NK cells) seems to be a key mechanism for the maternal-fetal intolerance in allogeneic pregnancy, and recurrent spontaneous abortion. The effect of expression of the NK cell activating receptor Ly49D recognizing BALB/c or DBA/2 class I MHC was investigated.


METHODS
Intracellular interleukin (IL)-100 production was detected and target cell survival rates were calculated after 22 hr coincubation of rat NK cells transfected, or not. with a murine Ly49D receptor, with either male BALB/c or male DBA/2 splenocytes, by using flow cytometry.


RESULTS
Ly49D negative rat NK cells produced 13.7% more IL-10 than Ly49D positive rat NK cells, and more splenocytes were killed by Ly49D transfected rat NK cells (survival rate 2.45%) than by Ly49D negative rat NK cells (survival rate 4.36%).


CONCLUSIONS
After physiological stimulation with BALB/c or DBA/2 splenocytes, rat NK cells are able to synthesize IL-10. Recognition of mouse splenocyte major histocompatibility complex (MHC) by Ly49D mice receptor decreased IL-10 production. The observed increase in killing activity might be a result of this phenomenon. NK cell activation via the Ly49D receptor might play an important role in pregnancy failure, but cannot explain why CBA/J X DBA/2 matings are abortion prone, and CBA/J X BALB/c matings are abortion resistant.
Neiss
J
J
Department of Obstetrics and Institute of Clinical Immunology, Friedrich-Schiller-Universitat, Jena, Germany.
Manuel
J
J
Markert
U R
UR
Clark
D A
DA
D000022:Abortion, Spontaneous / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011247:Pregnancy; D051381:Rats; D055630:Receptors, NK Cell Lectin-Like; D014162:Transfection
D000950:Antigens, Ly; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; C527092:Klra4 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D016753:Interleukin-10