The function of TGF-ß associated with proliferation of CD 16+ NK cell and CD16- NK cell in peripheral blood

Objective: We investigate the effects of TGF-ß on the growth of NK cells as well as on the proliferation of each subtype of NK cells, recognizing the fact that TGF-ß is the key player in inducing “immune tolerance” upon implantation in the uterus.

Materials and Methods: This study was prospectively designed. Blood donors including 5 healthy women. PBMCs containing the pbNK cell fraction were purified. After then the pbNK cells maintained in culture media (Myelocult medium (StemCell Technologies) for 14days. For experiments we added 5ng/ml recombinant human TGF-β1 (R&D system, USA) to pbNK cell. Two-color flow cytometric analysis were performed using FACS caliber flow cytometer.

Results: CD3-/CD16+56 NK cells showed a statistically significant increase after 14 days only in the control group(59.15±7.45 vs. 84.53±9.03, p=0.005, study group: 59.15±7.45 vs. 45.28±26.62, p=0.30). In addition, the proportion of CD3-/CD16+56 NK cells was shown to be significantly lower in the study group than in the control group (84.53±9.03 vs. 45.28±26.62, p=0.032).

The overall CD16- NK cell proportion was shown increased in both groups, but statistical significance was observed only in the study group (Control: 13.64±6.72 vs. 32.73±4.12,p=0.07, TGF-ß: 13.64±6.72 vs. 38.19 ± 15.74, p=0.023). The CD16+ NK cells was decrease in both groups, with statistical significance being displayed only by the study group (Control: 52.72±4.52 vs. 6.01±9.64,p=0.07, TGF-ß: 52.72±4.52 vs. 15.45 ±4.99, p=0.000).

Conclusion: The increase in the proportion of CD16- NK cells, which are crucial for implantation during early pregnancy, is not a result of reprogramming of CD16+ NK cells into CD16- NK cells, but a result of a relatively small decrease in the number of CD16+ NK cells accompanied by a relatively large increase in the number of CD16- NK cells, which is induced by TGF-ß that exists in the decidua during early pregnancy.