T Cell Apoptosis in Human Heart Allografts : Association with Lack of Co-Stimulation?
| Autor: | Van Hoffen, Els, Van Wichen, Dick F., Leemans, Jaklien C., Broekhuizen, Richard A.J.F., Bruggink, Annette H., De Boer, Mark, De Jonge, Nicolaas, Kirkels, Hans, Slootweg, Piet J., Gmelig-Meyling, Frits H.J., De Weger, Roel A. |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Graft Rejection
Time Factors Biopsy Myocardium T-Lymphocytes CD4-CD8 Ratio Apoptosis Immunohistochemistry Proto-Oncogene Proteins c-bcl-2 Antigens CD Proto-Oncogene Proteins Heart Transplantation Humans Fluorescent Antibody Technique Indirect In Situ Hybridization Regular Articles bcl-2-Associated X Protein |
| Popis: | It is unclear whether the intracardial immune reactivity after heart transplantation influences the peripheral immunological status (activation or nonresponsiveness) of the patient. Co-stimulation and activation-induced cell death (AICD) or apoptosis play an important role in determining the balance between lymphocyte reactivity and nonreactivity. Therefore, we studied the expression of co-stimulatory molecules and the process of apoptosis in biopsies of human heart allografts, using immunohistochemistry. Although a normal expression of co-stimulatory molecules on antigen-presenting cells was observed, the expression of their counter-structures on T cells was absent. This may be due to chronic T cell activation, which can lead to the induction of apoptosis via the Fas/Fas ligand pathway. In the infiltrates, a considerable percentage of the lymphocytes, but not the macrophages, were apoptotic. Apoptosis was confirmed by DNA fragmentation analysis. Increased numbers of Bax-expressing versus decreased numbers of Bcl2-expressing lymphocytes in comparison with normal lymphoid tissue confirmed a imbalance in favor of apoptosis. Apoptosis was biased towards CD4+ T cells (65.7% versus 26.6% in CD8+ T cells). Fas was expressed on most of the infiltrating cells. Fas ligand expression was also observed, not only on most of the T cells but also on all macrophages. Because macrophages were often detected in close contact with T cells, they may play a role in T cell regulation via the Fas/Fas ligand pathway. This study indicates that, during rejection, not only is tissue damage induced by infiltrating T cells, but also the infiltrating lymphocytes themselves are actively down-regulated (eg, AICD) by one another and by macrophages in the infiltrate. This regulatory process may affect the immunological status of the patient after heart transplantation. |
| Databáze: | OpenAIRE |
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