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C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells
  1. Johan Bäcklund1,
  2. Cuiqin Li1,2,
  3. Erik Jansson1,
  4. Stefan Carlsen1,
  5. Patrick Merky1,
  6. Kutty-Selva Nandakumar1,
  7. Sabrina Haag1,
  8. Jimmy Ytterberg3,
  9. Roman A Zubarev4,
  10. Rikard Holmdahl1
  1. 1Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
  2. 2Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xian, China
  3. 3Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
  4. 4Chemistry I Division, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
  1. Correspondence to Dr Johan Bäcklund, Medical Inflammation Research, Department of Medical Biochemistry & Biophysics, Scheeles väg 2, B2, plan 4, Karolinska Institute, Stockholm171 77, Sweden; johan.backlund{at}ki.se

Abstract

Introduction Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II Aq-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified.

Objective To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII.

Results Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2b-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of Aq on the C57BL/6 background induced T cell response to the CII260–270 epitope, and also prolonged the arthritis to be more chronic.

Conclusions The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing Aq, with which T cell determinants have been thoroughly characterised.

  • T Cells
  • Inflammation
  • Autoimmune Diseases

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