Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation

Transpl Immunol. 2008 Apr;19(1):69-73. doi: 10.1016/j.trim.2008.01.005. Epub 2008 Feb 22.

Abstract

CD4(+)CD25(high) T cells named regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. Interleukin-2 (IL-2) enhance the development of effector cells and is essential for generation of Treg cells. The effect of the anti-CD25 monoclonal antibody (anti-CD25mAb) induction therapy on the neogenetic CD4(+)CD25(high)Treg cells is important for therapeutic strategies in kidney transplant. To clarify the question, a prospective study was conducted in 21 living donor kidney transplant recipients who randomly divided into the anti-CD25mAb group (Daclizumab) with 11 patients and the control group with 10 patients. The frequency of CD4(+)CD25(high)Treg cells in total CD4(+) T cells was analyzed by flow cytometry and FoxP3 expression by RT-PCR in peripheral blood, and results were compared at day 0, 3, 13, 17, 27 posttransplantation. There was no significant difference in patient characteristics and allograft survival. The present study showed that in vivo antigen-specific Treg cells population were generated and expanded after transplant. Both groups showed a significant increase in the frequency of CD4(+)CD25(high)Treg cells and higher level of FoxP3 mRNA after transplantation while the serum creatinine declined. Compared with the control group, recipients with anti-CD25mAb injection had significantly lower percentage of CD4(+)CD25(high) in total CD4(+) cells (1.13%+/-0.13% vs 1.94%+/-0.22%, P=0.00; 3.75%+/-0.28% vs 7.11%+/-0.51%, P=0.00) on day 3, 17 after transplantation. While, the percentage was not significantly different on day 10, 27 (3.72%+/-0.19% vs 4.36%+/-0.28%, P=0.08; 7.84%+/-0.35% vs 8.56%+/-0.36%, P=0.16). However, there was not obvious difference in Foxp3 expression level associated with the source of the CD4(+)CD25(high)Treg cells at the different time point after transplant. Our data indicated that CD4(+)CD25(high)Treg cells were transiently affected by anti-CD25mAb, without depletion. In conclusion, the short-term treatment with anti-CD25mAb might not prevent the production, proliferation of neogenetic Treg cells in organ transplant.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized
  • CD4-Positive T-Lymphocytes / immunology
  • Daclizumab
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Kidney Transplantation / immunology*
  • Lymphocyte Count
  • Male
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transplantation Tolerance / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunoglobulin G
  • Interleukin-2 Receptor alpha Subunit
  • Daclizumab