Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies

Transpl Immunol. 2013 Jun;28(4):176-82. doi: 10.1016/j.trim.2013.04.005. Epub 2013 Apr 20.

Abstract

T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1 year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1 year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12 months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3 months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1 year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7-) were observed from baseline up to more than 1 year after transplantation. Rejection was associated with higher levels of these cells during the first 6 months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.

Keywords: Flow cytometry; Heart transplantation; Immune monitoring; Kinetics; Lymphocyte subset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Sectional Studies
  • Daclizumab
  • Female
  • Graft Rejection / drug therapy
  • Graft Rejection / immunology
  • Heart Transplantation*
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Interleukin-2 Receptor beta Subunit / biosynthesis
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-2 Receptor beta Subunit
  • Daclizumab