Calyculin A inhibits expression of CD8alpha but not CD4 in human peripheral blood T cells.
The CD8 glycoprotein serves as a coreceptor for T cell receptor (TCR)-mediated recognition of peptides associated to MHC class I. In CD8alpha deficiency, MHC class-I restricted cytotoxic T lymphocytes (CTL) are absent and lineage commitment to CD8 cells is impaired. We described a pharmacological approach to reduce the amount of CD8 surface glycoproteins on human peripheral blood T cells. Using calyculin A, a potent inhibitor of protein phosphatases, we were able to down regulate both CD8alpha protein and mRNA. Reduction of CD8alpha surface expression was dose- and time-dependent. The effect was specific to CD8alpha in that CD4 expression was not affected and specific for calyculin A. Okadaic acid, another phosphatase inhibitor did not show any influence on the expression of CD4 or CD8.
Allam
A
A
University of Konstanz, Faculty of Sciences, Department of Biology, Immunology, Germany.
Illges
H
H
D015153:Blotting, Western / Q000379:methods; D015704:CD4 Antigens / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D015704:CD4 Antigens; D016827:CD8 Antigens; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases