title: Death-inducing receptors and apoptotic changes in lymphocytes of patients with heart transplant vasculopathy.
abstract: 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.
authors.affiliation: Department of Surgery, General Hospital of Vienna University, Austria. hjankersmit@hotmail.com
authors.forename: H J
authors.initials: HJ
authors.lastname: Ankersmit
authors.forename: B
authors.initials: B
authors.lastname: Moser
authors.forename: S
authors.initials: S
authors.lastname: Roedler
authors.forename: I
authors.initials: I
authors.lastname: Teufel
authors.forename: A
authors.initials: A
authors.lastname: Zuckermann
authors.forename: G
authors.initials: G
authors.lastname: Roth
authors.forename: K
authors.initials: K
authors.lastname: Lietz
authors.forename: C
authors.initials: C
authors.lastname: Back
authors.forename: S
authors.initials: S
authors.lastname: Gerlitz
authors.forename: E
authors.initials: E
authors.lastname: Wolner
authors.forename: G
authors.initials: G
authors.lastname: Boltz-Nitulescu
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D016753:Interleukin-10; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1