Tim-3 and PD-1 regulate CD8+T cell function to maintain early pregnancy in mice.
During pregnancy, CD8+T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8+T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3+PD-1+CD8+T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy. Furthermore, normal pregnant CBA/J females challenged with Tim-3- and/or PD-1-blocking antibodies were more susceptible to fetal resorption. These findings indicate that Tim-3 and PD-1 pathways play critical roles in regulating CD8+T cell function and maintaining normal pregnancy.
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
Yuan-Yuan
YY
Xu
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
Song-Cun
SC
Wang
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
Yi-Kong
YK
Lin
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.|Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Da-Jin
DJ
Li
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.|Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Mei-Rong
MR
DU
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D020964:Embryo Loss; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*
C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
CD8+ T; Miscarriage; Pregnancy; Programmed cell death-1 (PD-1); T-cell immunoglobulin mucin-3 (Tim-3)