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Activation-induced T cell death, and aberrant T cell activation via TNFR1 and CD95-CD95 ligand pathway in stable cardiac transplant recipients
- Publication Year :
- 2002
- Publisher :
- Blackwell Science Inc, 2002.
-
Abstract
- SUMMARYSpecific blockade by antibodies (Abs) utilized in induction therapy may cause activation-induced cell death (AICD) in lymphocytes of transplant recipients, preactivated via CD95 and tumour necrosis factor-α receptor type 1 (TNFR1), and reduce allograft rejection frequency. Amongst 618 heart transplant (HTX) patients receiving antithymocytes globulin (ATG) therapy, 14 recipients with IVUS-verified freedom of transplant vasculopathy were studied. The control group contained 14 patients awaiting transplantation, classified by the New York Hearth Association heart failure as class IV. From 618 HTX patients 89% were free of rejection grade ISHLT ≥2–3 within 3-month post transplantation and 86% after one year. The death inducing receptors (DIR) such as CD95, CD95L and soluble TNFR1 were significantly increased in HTX recipients versus controls, as demonstrated by FACS, immunoblotting or ELISA (P < 0·001). The presence of increased DIR and in vivo apoptosis in HTX recipients, indicated by annexin-V binding, was further confirmed by the presence of high concentration of histones in the sera of patients. ATG, anti-IL-2R and OKT-3 Abs inhibited cell proliferation in a dose-dependent manner. The induction of apoptosis and/or necrosis was demonstrated in cells cultured with these Abs by annexin-V and 7-aminoactinomycin staining, respectively. Our findings demonstrate that T cells from HTX recipients express high level of CD95, CD95L and soluble TNFR1, and undergo apoptosis and AICD. These cells recognizing donor alloantigens may be selectively eliminated in vivo, and should be responsible for the observed immunological unresponsiveness, indicated by low rejection rates in our patient cohort treated by conventional triple therapy.
- Subjects :
- Adult
Graft Rejection
Necrosis
Fas Ligand Protein
medicine.medical_treatment
T cell
T-Lymphocytes
Immunology
Apoptosis
Lymphocyte Activation
Fas ligand
Antibodies
Receptors, Tumor Necrosis Factor
Histones
Immune system
Antigens, CD
medicine
Immunology and Allergy
Humans
fas Receptor
Annexin A5
Cells, Cultured
Antilymphocyte Serum
Retrospective Studies
Membrane Glycoproteins
business.industry
Receptors, Interleukin-2
Original Articles
Fas receptor
Transplantation
Cytokine
medicine.anatomical_structure
Receptors, Tumor Necrosis Factor, Type I
Heart Transplantation
Tumor necrosis factor receptor 1
medicine.symptom
business
Immunosuppressive Agents
Muromonab-CD3
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....23b4fb622a6cd18fc1f50723e4fb40d2