The appropriate frequency and function of decidual Tim-3+CTLA-4+CD8+ T cells are important in maintaining normal pregnancy

Songcun Wang, Fengrun Sun, Mengdie Li, Jinfeng Qian, Chunqin Chen, Mingyan Wang, Xingxing Zang, Dajin Li, Min Yu, Meirong Du

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Maternal decidual CD8+ T (dCD8+ T) cells must integrate the antithetical demands of maternal–fetal tolerance and anti-viral immunity to establish a successful pregnancy. T-cell immunoglobulin mucin-3 (Tim-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two important co-inhibitory molecules that regulating CD8+ T cells responses during infection and tumor. In the present study, we examined the co-expression of Tim-3 and CTLA-4 on CD8+ T cells during pregnancy and found the higher frequency of Tim-3+CTLA-4+dCD8+ T cells in response to trophoblasts. This Tim-3+CTLA-4+dCD8+ T cells subset showed an active status and produced more anti-inflammatory cytokines. Furthermore, the decreased number and altered function of Tim-3+CTLA-4+dCD8+ T cells correlated to miscarriage. Combined blocking Tim-3 and CTLA-4 pathways were highly effective in inhibiting the production of anti-inflammatory cytokines and were detrimental to the maintenance of pregnancy. Together, these findings supported that Tim-3 and CTLA-4 pathways might play positive roles in the establishment and/or maintenance of maternal–fetal tolerance so to promote the maintenance of normal pregnancy. So the reproductive safety must be considered, especially when anti-Tim-3/CTLA-4 antibody (and other immune checkpoint inhibitors) are used in pregnancy.

Original languageEnglish (US)
Article number407
JournalCell Death and Disease
Issue number6
StatePublished - Jun 1 2019

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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