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A failure in maternal immune tolerance to the fetus may result in abnormal pregnancies, such as recurrent spontaneous abortion. The regulation of T-cell homeostasis during pregnancy has important implications for maternal tolerance and immunity. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here we described the lower frequency of splenic T cells co-expressing CTLA-4 and Tim-3 accompanied by higher levels of proinflammatory but lower anti-inflammatory cytokines production in abortion-prone mouse model. Blockade of CTLA-4 and Tim-3 pathways leaded to the dysfunction of splenic T cells. By the higher expression during normal pregnancy, CTLA-4 and Tim-3 co-expression on splenic T cells linked to immunosuppressive phenotype. As the spleen is an important site for peripheral immune activation, our data suggest potential noninvasive biomarkers and therapeutic targets for miscarriage.<\/jats:p>","DOI":"10.1093\/biolre\/ioz076","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T19:33:52Z","timestamp":1556307232000},"page":"410-417","source":"Crossref","is-referenced-by-count":3,"title":["Altered frequency and function of spleen CTLA-4+Tim-3+ T cells are associated with miscarriage\u2020"],"prefix":"10.1093","volume":"104","author":[{"given":"Songcun","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiangFeng","family":"Ye","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dajin","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Qian","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meirong","family":"Du","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, P.R. 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