Increased expression of cytotoxic effector molecules: different interpretations for steroid-based and steroid-free immunosuppression

Pediatr Transplant. 2003 Feb;7(1):53-8. doi: 10.1034/j.1399-3046.2003.02053.x.


Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid-based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post-transplantation as well as with different immunosuppression protocols (steroid-based or steroid-free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non-invasive method of quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid-free and steroid-based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post-transplantation and for graft function at 1 yr post-transplantation in a separate clinical study. Steroid-free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post-transplantation with the increase being seen largely by the first post-transplant month. A further increase in GL expression was noted at the end of the first post-transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time-points post-transplantation, CTL genes were found to be higher in steroid-free patients with stable graft function, compared to steroid-based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid-based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid-free immunosuppression. The early increase in levels seen in steroid-free patients appears to correlate with the total absence of steroids. As steroid-free patients seem to have a lower incidence of acute rejection and better long-term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Child
  • Cytotoxicity, Immunologic
  • Daclizumab
  • Gene Expression / drug effects
  • Graft Rejection / metabolism
  • Granzymes
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tacrolimus / pharmacology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Differentiation, T-Lymphocyte
  • GNLY protein, human
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Daclizumab
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • Mycophenolic Acid
  • Tacrolimus