IFN-γ-producing effector CD8 T lymphocytes cause immune glomerular injury by recognizing antigen presented as immune complex on target tissue

Ken Tsumiyama, Akira Hashiramoto, Mai Takimoto, Sachiyo Tsuji-Kawahara, Masaaki Miyazawa, Shunichi Shiozawa

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Abstract

We investigated the role of effector CD8 T cells in the pathogenesis of immune glomerular injury. BALB/c mice are not prone to autoimmune disease, but after 12 immunizations with OVA they developed a variety of autoantibodies and glomerulonephritis accompanied by immune complex (IC) deposition. In these mice, IFN-γ-producing effector CD8 T cells were significantly increased concomitantly with glomerulonephritis. In contrast, after 12 immunizations with keyhole limpet hemocyanin, although autoantibodies appeared, IFN-γ-producing effector CD8 T cells did not develop, and glomerular injury was not induced. In β2-microglobulin-deficient mice lacking CD8 T cells, glomerular injury was not induced after 12 immunizations with OVA, despite massive deposition of IC in the glomeruli. In mice containing a targeted disruption of the exon encoding the membrane-spanning region of the Ig μ-chain (μMT mice), 12 immunizations with OVA induced IFN-γ- producing effector CD8 T cells but not IC deposition or glomerular injury. When CD8 T cells from mice immunized 12 times with OVA were transferred into naive recipients, glomerular injury could be induced, but only when a single injection of OVA was also given simultaneously. Importantly, injection of OVA could be replaced by one injection of the sera from mice that had been fully immunized with OVA. This indicates that deposition of IC is required for effector CD8 T cells to cause immune tissue injury. Thus, in a mouse model of systemic lupus erythematosus, glomerular injury is caused by effector CD8 T cells that recognize Ag presented as IC on the target renal tissue.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalJournal of Immunology
Volume191
Issue number1
DOIs
Publication statusPublished - Jul 1 2013

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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