Interleukin-2, but not interleukin-15, is required to terminate experimentally induced clonal T-cell anergy.
It has been demonstrated that T cells stimulated with nucleosome-polyomavirus T-antigen (self-nonself) complexes, but not nucleosomes, activate autoimmune nucleosome-specific T cells. As these cells may be naïve, such observations do not show that anergic T cells are reactivated. To understand the regulation of autoimmunity, this is important to assess, and this is the focus of this study. T-cell anergy was induced by antigen stimulation in the presence of antibodies to the costimulatory molecules CD80/CD86. Requirements for the reactivation of anergic T cells were analysed by the ability of antigen and interleukin-2 (IL-2) or IL-15 to increase T-cell proliferation and IL-2 transcription. Data demonstrate that stimulation of T cells with T-antigen and anti-CD80/86 antibodies promotes long-lasting clonal T-cell anergy. While T-antigen did not reactivate anergic T cells, proliferation and upregulation of IL-2 gene transcription was initiated by stimulation with antigen, costimulation and IL-2 added to the cultures. Proliferation per se was not sufficient to promote the reactivation of anergic T cells, as both IL-2 and IL-15 induced proliferation, while antigen and IL-2, but not IL-15, upregulated IL-2 mRNA levels. These data demonstrate that the innate immune system and IL-2 are central to the initiation and termination of T-cell anergy.
Bendiksen
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Department of Biochemistry, Institute of Medical Biology, Medical Faculty, University of Tromsø, N-9037 Tromsø, Norway.
Rekvig
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D015703:Antigens, CD / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000276:immunology; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D002455:Cell Division / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D000957:Antigens, Viral, Tumor; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012313:RNA