Interleukin‐2, But Not Interleukin‐15, is Required to Terminate Experimentally Induced Clonal T‐Cell Anergy

• Published in: Scandinavian journal of immunology 2004-08, Vol.60 (1‐2), p.64-73
• Main Authors: Bendiksen, S., Rekvig, O. P.
• Format: Article
• Language: English
• Subjects: Antigens, CD - immunology; Antigens, Viral, Tumor - immunology; B7-1 Antigen; B7-2 Antigen; Cell Division - immunology; Clonal Anergy - immunology; Humans; Interleukin-15 - genetics; Interleukin-15 - immunology; Interleukin-2 - genetics; Interleukin-2 - immunology; Lymphocyte Activation - immunology; Membrane Glycoproteins - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA - chemistry; RNA - genetics; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.0300-9475.2004.01446.x

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.