A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejection after transplantation

Clin Immunol. 2010 Nov;137(2):209-20. doi: 10.1016/j.clim.2010.07.008. Epub 2010 Sep 6.

Abstract

Regulatory T cells (Tregs) are known to suppress alloimmune responses during pregnancy and post organ transplantation. We demonstrate that a distinct subset of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool is critically involved in preterm labor induction and kidney transplant rejection as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but that the level of HLA-DR expression of such Tregs was strongly diminished in preterm laboring women and in patients with acute renal allograft rejection. In addition, both patient collectives showed a significantly reduced suppressive activity of their circulating CD4(+)CD127(low+/-)CD25(+)-Treg cell pool. Our findings propose that the FoxP3(+)DR(+)-Treg subset may be decisively responsible for the suppressive activity of the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool and that the immunologic mechanisms leading to preterm labor necessitating preterm delivery may be similar to those leading to allograft rejection after transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • Female
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / immunology*
  • HLA-DR Antigens / immunology*
  • Humans
  • Immune Tolerance / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Kidney Transplantation / immunology
  • Male
  • Obstetric Labor, Premature / immunology*
  • Obstetric Labor, Premature / physiopathology*
  • Pregnancy
  • Premature Birth / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-DR Antigens
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit