Defective de novo thymocyte maturation in cyclosporin A (CsA)-induced autoimmunity : expression of costimulatory and activation molecules

Lethally x-irradiated Lewis rats, reconstituted with syngeneic bone marrow and transiently treated with CsA for 4 weeks, will develop an autoimmune disease about 2-3 weeks after cessation of CsA therapy. CsA-induced autoimmunity is a thymus-dependent and T cell-mediated autoimmune disease. CsA is th...

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Bibliographic Details
Published in:Clinical and experimental immunology 1997-10, Vol.110 (1), p.79-85
Main Authors: HOMMA, M, VAN BREDA VRIESMAN, P. J. C, DAMOISEAUX, J. G. M. C
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - immunology
Autoimmunity
Biological and medical sciences
Cyclosporine - administration & dosage
Cyclosporine - immunology
Experimental and animal immunopathology. Animal models
Female
Flow Cytometry
Immunopathology
Lymphocyte Activation
Medical sciences
Rats
Rats, Inbred Lew
T-Lymphocytes - immunology
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Summary:Lethally x-irradiated Lewis rats, reconstituted with syngeneic bone marrow and transiently treated with CsA for 4 weeks, will develop an autoimmune disease about 2-3 weeks after cessation of CsA therapy. CsA-induced autoimmunity is a thymus-dependent and T cell-mediated autoimmune disease. CsA is thought to generate autoreactive T cells by interference with negative selection in the thymus; x-irradiation is required to eliminate the peripheral autoregulatory T cell circuit. In this study we re-evaluate the effect of CsA on thymic atrophy and thymocyte maturation. Subsequently we examine the expression of costimulatory and activation molecules (CD2, CD5, CD11a, CD11b, CD25, CD28, CD43, CD54, OX-40, RT-1A, RT-1B and RT-1D) during distinct maturational stages in order to detect possible clues to the observed effects of CsA on thymocyte maturation and selection. The results revealed that CsA blocks maturation of double-positive TCR(int) to double-positive TCR(high) thymocytes and preferentially inhibits the development of mature CD4 single-positive thymocytes. Furthermore, CsA administration resulted in a reduced expression of the costimulatory CD2 molecule. Although it is a matter of debate whether this defective CD2 expression is involved in the aberrant maturation and selection of thymocytes, it is speculated that reduced costimulation via CD2 may influence differentiation into distinct T cell subsets.
ISSN:0009-9104
1365-2249
DOI:10.1046/j.1365-2249.1997.5001397.x