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
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PROBLEM: 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. METHOD OF STUDY: Intracellular interleukin (IL)‐10 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%). CONCLUSION: 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.
