Interleukin-12 augments cytolytic activity of peripheral and decidual lymphocytes against choriocarcinoma cell lines and primary culture human placental trophoblasts

PROBLEM: Human trophoblasts are tolerant to the maternal immune system, but susceptible to interleukin (IL)-2-activated lymphocytes. IL-12 is also a key cytokine in the induction of cytotoxic responses. We administered IL-12 to peripheral blood lymphocytes (PBLs) and to decidual lymphocytes (DLs) and studied resulting cytotoxicity against trophoblasts. METHOD OF STUDY: PBLs and DLs were stimulated with rIL-2 and/or rIL-12 for 48 hr in vitro. Cytotoxicity against the choriocarcinoma cell line JEG-3, JAR, and primary culture trophoblasts were examined by LDH release assay. The proliferative response was estimated by MTT assay. Expression of cytotoxic factors was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Whereas IL-12 alone produced a modest enhancement in cytotoxicity of PBLs and DLs, the combination of IL-2 and IL-12 was most effective in trophoblast cell lysis. IL-12 enhanced the mRNA expression of T-cell specific serine protease (TSP, granzyme B) and Fast in DLs, but the expression of perforin was unchanged. Expression of these cytotoxic factors in PBLs was up-regulated by IL-12. CONCLUSION: Our findings indicate critical roles of IL-12 in the activation of maternal lymphocytes, which could possibly result in pregnancy failure syndromes.