T cell activation by concanavalin A in the presence of cyclosporin A: immunosuppressor withdrawal induces NFATp translocation and interleukin-2 gene transcription.
Cyclosporin A (CSA), an immunosuppressive agent used in organ transplantation and to treat some autoimmune diseases, blocks the Ca2+-dependent steps involved in T cell receptor triggering leading to interleukin (IL)-2 production. Considering that the early steps of T cell activation are insensitive to CSA, we asked whether the initial activation achieved in presence of this immunosuppressor could affect the capacity of the T cell to respond to a mitogenic restimulation. We found that T cells activated by concanavalin A (ConA) for 48 h in the presence of CSA retain the capacity to proliferate in response to ConA once the immunosuppressor is removed. These cells are able to transcribe anew the IL-2 gene, without the requirement of new protein synthesis, and to up-regulate the alpha chain of the IL-2 receptor. Furthermore, we present the first direct evidence that the nuclear factor AP-1 is present in the nucleus of the T cells primed for 48 h in presence of CSA and that withdrawal of the immunosuppressor leads to the translocation of NFATp from the cytoplasm to the nucleus.
Bemer
V
V
Immunophysiologie Moléculaire, Institut Pasteur, Paris, France.
Truffa-Bachi
P
P
D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology*
D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D003208:Concanavalin A; D016572:Cyclosporine