Upregulation of Tim-3 expression at feto-maternal interface may explain embryo survival in the CBAxDBA/2 model of abortion.

PROBLEM

To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system.

METHODS OF STUDY

Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively.

RESULTS

The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4.

CONCLUSION

Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.