Article (Scientific journals)
Cyclosporin-A differentially affects apoptosis during in vivo rat thymocyte maturation
Damoiseaux, JGMC; Defresne, Marie-Paule; Reutelingsperger, C. P. M. et al.
2002In Scandinavian Journal of Immunology, 56 (4), p. 353-360
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Abstract :
[en] Maturation arrest and interference with selection are two well-documented effects of cyclosporin-A (CsA) on the thymus. We recently hypothesized that these effects are related and owing to the reduced T-cell receptor (TCR)-CD3 complex-mediated signal transduction in thymocytes upon CsA treatment. In this hypothesis, the maturation arrest is the result of the additional depletion of thymocytes that normally survive by positive selection, whereas the impaired self-tolerance induction is caused by an increased survival of thymocytes that normally undergo negative selection. In this view, it is anticipated that CsA differentially affects thymocyte apoptosis during in vivo thymocyte maturation. Indeed, we report in this study a strong increase in apoptotic cells in the thymic cortex on in situ analysis. Simultaneously, the number of apoptotic cells had decreased at the cortico-medullary zone which is held to be the site for negative selection. Rapamycin (Rapa) also interferes with thymocyted maturation by inhibiting cytokine-driven proliferation. Hence, Rapa preferentially affects the early maturational stages of thymoctye development and is considered not to alter thymocyte selection and subsequent apoptotic events. Indeed, the number of apoptotic events appears not to be altered. However, possibly owing to the decrease in cortical macrophages, the apoptotic cells revealed an atypical enumeration around blood vessels. Taken together, our results favour the hypothesis that the dominant effect of CsA on the thymus is the reduction of the TCR-CD3 complex-mediated signal transduction in thymocytes upon interaction with stromal cells. Furthermore, the preferential localization of apoptotic cells next to blood vessels upon Rapa administration may indicate that endothelial cells are a back-up system for the removal of apoptotic cells.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Damoiseaux, JGMC
Defresne, Marie-Paule ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie
Reutelingsperger, C. P. M.
Vriesman, PJCV
Language :
English
Title :
Cyclosporin-A differentially affects apoptosis during in vivo rat thymocyte maturation
Publication date :
October 2002
Journal title :
Scandinavian Journal of Immunology
ISSN :
0300-9475
eISSN :
1365-3083
Publisher :
Blackwell Publishing Ltd, Oxford, United Kingdom
Volume :
56
Issue :
4
Pages :
353-360
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 November 2010

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