Characterization of T follicular helper cells in allogeneic normal pregnancy and PDL1 blockage-induced abortion

Sci Rep. 2016 Nov 7:6:36560. doi: 10.1038/srep36560.

Abstract

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-1hi and CD4+CXCR5hiICOShi Tfh 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Induced / methods
  • Animals
  • B-Lymphocytes / immunology
  • B7-H1 Antigen / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Pregnancy
  • Receptors, CXCR5 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • B7-H1 Antigen
  • Receptors, CXCR5