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

OBJECTIVE

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.

METHODS

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 FasL in DLs, but the expression of perforin was unchanged. Expression of these cytotoxic factors in PBLs was up-regulated by IL-12.

CONCLUSIONS

Our findings indicate critical roles of IL-12 in the activation of maternal lymphocytes, which could possibly result in pregnancy failure syndromes.