C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells

• INTRODUCTION: Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-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-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) 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 A(q), with which T cell determinants have been thoroughly characterised.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

Animals

Arthritis

Experimental/*genetics/immunology

Arthritis

Rheumatoid/*genetics/immunology

Chickens

Collagen Type II/*immunology

*Disease Models

Animal

Epitopes

T-Lymphocyte/immunology

Genes

MHC Class II/*genetics

Haplotypes

Immunization

Mice

Mice

Congenic

Mice

Inbred C57BL

Mice

Inbred Strains

Mycobacterium/immunology

Rats

T-Lymphocytes/*immunology

Autoimmune Diseases

Inflammation

T Cells

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)