title: Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin.
abstract: The expression of CD5 can be induced on murine B-2 cells by anti-IgM, a recognized analog of thymus-independent 2 type (TI-2) antigen. Given that cyclosporin A (CsA) sensitivity is a distinguishing feature of TI-2 type B cell activation, we asked whether the in vitro induction of CD5 on B cells by anti-mu is CsA sensitive. We report that anti-mu induced CD5 expression on B-2 cells was inhibited by CsA as well as FK-520 and rapamycin. When L-685,818, a FK-520 and rapamycin antagonist, was added to anti-mu stimulated B cell cultures containing FK-520 or rapamycin, but not CsA, suppression was abrogated and complete induction of CD5 was seen. When we used either CD4+CD8+ thymocytes or peripheral T cells activated by phorbol ester and ionomycin, the cell surface induction of CD5 was also partially blocked by CsA, FK-520 and rapamycin. Moreover, in both B and T cells, the same immunosuppressive drugs did not affect constitutive CD5 expression but only blocked de novo induction. To determine the level of CD5 regulation, we activated T cells using phorbol myristate acetate (PMA)/ionomycin and report that CD5 induction was sensitive to actinomycin D (AcD). Similarly, the induction of CD5 on anti-mu activated B cells was blocked by AcD. In addition, T cells that were activated by PMA/ionomycin expressed more abundant CD5 mRNA than CsA or FK-520 treated cells. Based on the CsA-sensitive regulation of CD5 we thought that the CsA-sensitive nuclear factor of activated T cells (NFAT) might be involved in CD5 regulation. We report evidence by Western blot analysis that NFATp is expressed by both resting and TI activated B cells but apparently not CD4+CD8+CD5+ thymocytes. We conclude that in both B and T cells the induction of CD5 requires transcriptional regulation, and that the inhibition of CD5 expression by the immunosuppressive drugs CsA, FK-520 and rapamycin requires drug-immunophilin complex formation.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: M
authors.initials: M
authors.lastname: Teutsch
authors.forename: M
authors.initials: M
authors.lastname: Higer
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: H W
authors.initials: HW
authors.lastname: Wortis
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018956:CD5 Antigens; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D016572:Cyclosporine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011090:Polyenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020123:Sirolimus; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D018956:CD5 Antigens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011090:Polyenes; D014157:Transcription Factors; C044203:anti-IgM; C076383:L 685818; D015759:Ionomycin; D016572:Cyclosporine; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D020123:Sirolimus; D016559:Tacrolimus