Publication Date:
1988-09-23
Description:
Cyclosporine A (CsA) is an important immunosuppressive drug that is widely used in transplantation medicine. Many of its suppressive effects on T cells appear to be related to the inhibition of T cell receptor (TCR)-mediated activation events. Paradoxically, in certain situations CsA is responsible for the induction of a T cell-mediated autoimmunity. The effects of CsA on T cell development in the thymus were investigated to elucidate the physiologic events underlying this phenomenon. Two major effects were revealed: (i) CsA inhibits the development of mature single positive (CD4+8- or CD4-8+) TCR-alpha beta+ thymocytes without discernibly affecting CD4-8- TCR-gamma delta+ thymocytes and (ii) CsA interferes with the deletion of cells bearing self-reactive TCRs in the population of single positive thymocytes that do develop. This suggests a direct mechanism for CsA-induced autoimmunity and may have implications for the relative contribution of TCR-mediated signaling events in the development of the various T cell lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jenkins, M K -- Schwartz, R H -- Pardoll, D M -- New York, N.Y. -- Science. 1988 Sep 23;241(4873):1655-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3262237" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Monoclonal
;
Antigens, Differentiation, T-Lymphocyte/genetics
;
Autoimmune Diseases/chemically induced
;
Cell Differentiation/drug effects
;
Cyclosporins/*pharmacology
;
Mice
;
Mice, Inbred Strains
;
Receptors, Antigen, T-Cell/drug effects/genetics
;
T-Lymphocytes/*drug effects/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
