Death-inducing receptors and apoptotic changes in lymphocytes of patients with heart transplant vasculopathy

Clin Exp Immunol. 2002 Jan;127(1):183-9. doi: 10.1046/j.1365-2249.2002.01741.x.


The specific role of lymphocyte apoptosis and transplant-associated atherosclerosis is not well understood. The aim of our study was to investigate the impact of T cell apoptotic pathways in patients with heart transplant vasculopathy. Amongst 40 patients with cardiac heart failure class IV who have undergone heart transplantation, 20 recipients with transplant-associated coronary artery disease (TACAD) and 20 with non-TACAD were investigated one year postoperative. Expression of CD95 and CD45RO, and annexin V binding were measured by FACS. Soluble CD95, sCD95 ligand (sCD95L), tumour necrosis factor receptor type 1 (sTNFR1), and histones were measured in the sera by ELISA. The percentage of cells expressing CD3 and CD4 was significantly reduced in TACAD as well as in non-TACAD patients as compared with control volunteers. Interestingly, the proportion of CD19+ (B cells) and CD56+ (NK) cells was increased in TACAD groups (versus non-TACAD; P < 0.01, and P < 0.001, respectively). In contrast to sCD95, the expression of CD95 (APO-1/Fas) and CD45RO (memory T cells), and sCD95L were significantly increased in non-TACAD and TACAD patients. T cell activation via CD95 with consecutive apoptosis was increased in both groups. The concentration of sTNFR1, IL-10 and histones was significantly elevated in sera from TACAD than non-TACAD patients, and in both groups than in healthy controls. These observations indicate that the allograft may induce a pronounced susceptibility of CD4+ T cells to undergo apoptosis and antibody-driven activation-induced cell death. This data may suggest a paradox immune response similar to that seen in patients with autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / immunology*
  • Coronary Artery Disease / pathology*
  • Fas Ligand Protein
  • Female
  • Heart Transplantation* / adverse effects
  • Humans
  • Interleukin-10 / immunology
  • Leukocyte Common Antigens / immunology
  • Male
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptors, Tumor Necrosis Factor / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology*
  • Transplantation Immunology
  • Transplantation, Homologous / immunology
  • fas Receptor / immunology


  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • fas Receptor
  • Interleukin-10
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1