Publication: Cyclosporin A-induced changes of the thymic microenvironment. A review of morphological studies
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Date
1998
Authors
Milicevic, N.M. ; Milicevic, Z.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Cyclosporin A is an immunosuppressive
drug, which disrupts the activation of peripheral Tlymphocyte
pool and blocks the maturation of thymocytes
within the thymus. Normally, thymic nonlymphoid
cells provide the optimal inductive microenvironment
for development of T-lymphocytes. After application of
cyclosporin A the complex alterations of the thymic
microenvironment occur, affecting all types of
nonlymphoid cells.
All subsets of thymic epithelial cells are thoroughly
changed. The subcapsular epithelial cells show the
proGinent enlargement of cytokeratin contents. In
electron microscopy, however, these cells present the
morpho-functional aspect of resting cells. The epithelial
cells in deeper cortex become enlarged and stockier,
whereby their cell processes appear more ramified and
thicker. Thus, the cytoreticulum they create seems much
denser. These cells strongly express MHC antigens.
Their subcellular organization is suggestive of increased
synthetic and secretory activity. The number of
medullary epithelial cells is decreased. The cells with the
most mature phenotype are the most prominently
depleted and the ones with phenotypically and
morphologically immature appearance predominate.The
number of Hassall's bodies is also decreased.
The number of cortical macrophages does not
increase. However, these cells become enlarged showing
the prominent changes in enzyme capacity, histochemical
features and ultrastructural organization. Thus,
they become similar to macrophages located in the
cortico-medullary zone of the normal rat thymus.
Cortical macrophages increase the activity of hydrolytic
enzymes, acid phosphatase and nonspecific esterase,
develop the strong activity of chloroacetate esterase, the
strong activity of respiratory enzyme succinic dehydrogenase
and begin to show the marked presence of
prostaglandin synthase. Moreover, the cytoplasmic
inclusions, which are aldehyde fuchsin- and PASpositive
and show sudanophilia, appear within cortical
macrophages. In electron microscopy these cells show
Offprint requests to: Prof. Dr. Novica Milcevk, Dim. Tucovka 83, 11000
Beograd. Yugoslavia
an abundant cytoplasm a very active appearance and the
variety of vacuolar cytoplasmic inclusions. The mitoses
of neighboring thymocytes are often seen. The number
of interdigitating cells is decreased due to reduced size
of thymic medulla, but these cells do not show the
substantial phenotypic changes.
The description and classification of all types of
nonlymphoid cells, which constitute the normal thymic
microenvironment, is also presented. The functional
significance and possible mechanisms of CSA-induced
changes of the thymic microenvironment are discussed.
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