Human miscarriage is associated with increased number of CD26+ decidual lymphocytes

Abstract

Dipeptidyl peptidase-IV (DPP-IV, CD26), a serine protease with broad distribution in mammalian tissues and known activity in serum, participates in T-cell activation and promotes a Th1-like cytokine response. Previous data on murine abortion indicate that DPP-IV may play a critical role in pregnancy failure by inducing a Th1 local response. Here, we investigated the possible participation of DPP-IV in the onset of human spontaneous abortion (SA). The systemic (peripheral blood) and local (decidua) percentages of CD4+, CD8+, CD26+ and CD56+ cells as well as the number of Th1 lymphocytes (CCR5 cells) were assessed in samples from women after SAs (n = 20) and from women with normally progressing pregnancies (NPs) (n = 27) using flow cytometry and immunohistochemistry. We further measured the DPP-IV activity and concentrations of Th1 (interferon-γ and tumour necrosis factor-α), Th2 [interleukin-4 (IL-4), IL-10] and Th3 (transforming growth factor-β2) cytokines in serum samples. We could not find any difference in the number of CD4+, CD8+, CD26 +, CD26+/CD4+ or CD8+/CD26 + blood cells between NP and SA patients. No differences in the Th1, Th2 or Th3 cytokine levels could be observed between both groups. However, the percentages of decidual CD26+ lymphocytes as well as the number of decidual Th1 cells were significantly higher in SA samples compared to samples from patients with NP. Our data support the hypothesis that CD26+ decidual lymphocytes with DPP-IV activity may play a critical role in SAs, as previously suggested in an abortion mice model. This abortive effect may be mediated by enhancing the levels of Th1 abortogenic cytokines only locally.