Immunoregulation of IL-2 and IL-15 on the phenotype and function of NK subsets in PBMC and mixed lymphocyte culture

Objective To investigate the immunoregulation of IL 2 and IL 15 on the phenotype and function of NK subsets in PBMC and mixed lymphocyte culture. Methods The phenotypic changes of NK cells in human peripheral mononuclear cell (PBMC) and mixed lymphocyte culture (MLC) in the presence of IL 2 or IL 15 were detected by double fluorescent staining and flow cytometry. 51 Cr release assay was employed to measure the specific lysis of NK cells killing target K562 cells. Results Both IL 2 and IL 15 could increase the ratios of NK cells in PBMC and MLC. In addition, IL 15 was more effective than IL 2 in improving the proliferation of CD56 bright NK subsets in PBMC while IL 2 was more effective than IL 15 in increasing the number of CD56 bright NK subsets in MLC when 50 U/mL IL 2 or IL 15 was added at the beginning of the culture. The cytotoxicity of NK cells in PBMC culture and MLC were greatly enhanced by the addition of IL 2 or IL 15 with a dose dependent manner. Furthermore, IL 15 was more powerful than IL 2 at 50 U/mL in enhancing the cytotoxicity of NK cells in PBMC, whereas IL 2 was more powerful than IL 15 in enhancing the cytotoxicity of NK cells in MLC at the same concentration. When 50 U/mL IL 15 and 50 U/mL IL 2 were added,the cytotoxicity of NK cells was higher than that of the cells cultured only with IL 15 or IL 2 at the same concentration. Conclusion IL 15 is more effective than IL 2 in upregulating the proliferation of CD56 bright NK subsets and cytotoxicity of resting NK cells at low concentration while IL 2 is more effective than IL 15 in improving the proliferation of CD56 bright NK subsets and cytotoxicity of MLC gene rated NK cells at certain concentration. The different pattern of immunomodulation by IL 2 or IL 15 on NK cells may be due to the different expression of IL 2R or/and IL 15R on NK cells in the given condition or other cytokines presented in the culture forming a cytokine net work.