Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1002/art.10762 |
| Title (Primary) | Identification and characterization of SmD183-119-reactive T cells that provide T cell help for pathogenic anti-double-stranded DNA antibodies |
| Author | Riemekasten, G.; Langnickel, D.; Ebling, F.M.; Karpouzas, G.; Kalsi, J.; Herberth, G.
; Tsao, B.P.; Henklein, P.; Langer, S.; Burmester, G.R.; Radbruch, A.; Hiepe, F.; Hahn, B.H. |
| Source Titel | Arthritis and Rheumatism |
| Year | 2003 |
| Department | IMMU |
| Volume | 48 |
| Issue | 2 |
| Page From | 475 |
| Page To | 485 |
| Language | englisch |
| Abstract | Objective The C-terminal peptide of amino acids 83-119 of the SmD1 protein is a target of the autoimmune response in human and murine lupus. This study was undertaken to test the hypothesis that SmD183-119-reactive T cells play a crucial role in the generation of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies. Methods Splenic or lymph node T cells derived from unmanipulated as well as SmD183-119-immunized NZB/NZW mice were analyzed in vitro by enzyme-linked immunospot (ELISpot) assay to determine T cell help for anti-dsDNA generation induced by the SmD183-119 peptide. Cytokines expressed by these T cells were measured by ELISpot assay, enzyme-linked immunosorbent assay, and flow cytometry. SmD183-119- and ovalbumin-specific T cell lines were generated and characterized. Results The SmD183-119 peptide, but not the control peptides, significantly increased the in vitro generation of anti-dsDNA antibodies in cultures from unmanipulated NZB/NZW mice. Interferon- (IFN), interleukin-2 (IL-2), IL-4, transforming growth factor , and IL-10 production increased in response to the peptide in young mice; only IFN and IL-2 were increased in older, diseased mice. Activation of SmD183-119-reactive T cells by immunization of NZB/NZW mice resulted in elevated anti-dsDNA synthesis and, later, increased antibodies to SmD183-119. Most cells in SmD183-119-specific CD4+ T cell lines helping both antibodies had increased intracellular expression of IFN, and most expressed both IFN and IL-4. Conclusion The SmD183-119 peptide plays an important role in generating T cell help for autoantibodies, including anti-dsDNA, and activates different subsets of T cells as defined by distinct cytokine expression. This peptide is an interesting target structure for the modulation of autoreactive T cells, and its characterization may contribute to our understanding of the role of autoantigen-reactive T cells in the pathogenesis of SLE. |
| Riemekasten, G., Langnickel, D., Ebling, F.M., Karpouzas, G., Kalsi, J., Herberth, G., Tsao, B.P., Henklein, P., Langer, S., Burmester, G.R., Radbruch, A., Hiepe, F., Hahn, B.H. (2003): Identification and characterization of SmD183-119-reactive T cells that provide T cell help for pathogenic anti-double-stranded DNA antibodies Arthritis Rheum. 48 (2), 475 - 485 10.1002/art.10762 |
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