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T cell apoptosis in human heart allografts: association with lack of co-stimulation?
- Source :
-
The American journal of pathology [Am J Pathol] 1998 Dec; Vol. 153 (6), pp. 1813-24. - Publication Year :
- 1998
-
Abstract
- 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.
- Subjects :
- Antigens, CD metabolism
Biopsy
CD4-CD8 Ratio
Fluorescent Antibody Technique, Indirect
Graft Rejection pathology
Heart Transplantation immunology
Humans
Immunohistochemistry
In Situ Hybridization
Myocardium immunology
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
T-Lymphocytes pathology
Time Factors
bcl-2-Associated X Protein
Apoptosis
Graft Rejection immunology
Heart Transplantation pathology
Myocardium pathology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 153
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 9846972
- Full Text :
- https://doi.org/10.1016/S0002-9440(10)65696-9