Characterization of T follicular helper cells in allogeneic normal pregnancy and PDL1 blockage-induced abortion.
A deeper understanding of the immunological events during pregnancy will provide novel insights into the pathogenesis of pregnancy complications. The fundamental function of T follicular helper (Tfh) cells is to provide cognate help to B cells. Dysregulations of Tfh-cell function and/or development can result in various immunological diseases. However, the role and characteristics of Tfh cells during pregnancy remain unknown. Herein, an allogeneic-normal-pregnant mouse model was used, and we found that the CD4+T cells residing at the uterus and placenta (UP) displayed a Tfh-like phenotype; and the UP-derived CD4+CXCR5hiPD-1hiand CD4+CXCR5hiICOShiTfh cells, which showed a memory/activation phenotype, reached their peak at mid-pregnancy. These Tfh cells were located abundantly in the uterus at mid-pregnancy, but greatly increased in the placenta at late-pregnancy. Furthermore, increased foetal resorption by PDL1 blockade correlated with enhanced accumulation of Tfh cells and upregulated expressions of ICOS and PD-1 on these cells. Collectively, our findings are the first to indicate that an adequate and balanced accumulation of Tfh cells during gestation is likely to help maintaining a successful pregnancy, whereas an excessively high level of these cells could lead to abortion.
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Weihong
W
Zeng
Department of Dermatology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.
Zhicui
Z
Liu
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Siming
S
Zhang
Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P. R. China.
Jiabin
J
Ren
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Xiaoling
X
Ma
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Chuanmei
C
Qin
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Fuju
F
Tian
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China.
Yan
Y
Zhang
Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, the International Peace Maternity &Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
Yi
Y
Lin
D000028:Abortion, Induced / Q000379:methods; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D054380:Receptors, CXCR5 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D060890:B7-H1 Antigen; D054380:Receptors, CXCR5