IMMUNOGENETICS OF COLLAGEN-INDUCED ARTHRITIS

  • David, Chella S (PI)

Project: Research project

Project Details

Description

Arthritis will be induced in mice by intradermal injection of Chick,
Bovine, Rat, or Mouse Type II collagen. Assessment of arthritis in the
mouse will be accomplished by clinical inspection of the animals,
measurement of joint swelling, X-ray and histological analysis of the
joints. The genetics of CIA will be studied using inbred mice with varying
background genes, independent haplotype mice congenic to the C57BL/10,
C57GL/6, and C3H background, recombinant strains, and mutants. The
inheritance of the disease will be studied by F1, F2 and backcross
combinations. The humoral response to Type II collagen will be assessed in
relation to CIA. The level of IgG and IgM antibodies will be measured by
radio-immunoassay. Antisera will be investigated for cross-reactivity and
auto-reactivity against the four species of Type II collagen. The cellular
response to Type II collagen will be assessed in relation to CIA, with both
the in vitro (T-cell proliferation) and the in vivo (radiometric ear assay)
responses being monitored. The various subpopulations of cells involved in
the response will be identified. Passive transfer of CIA will be
investigated using cell and immunoglobulin transfer. This may elucidate
the contribution of various cell and antibody responses to collagen
relevant in the disease. Precise epitope specificity for different
collagen antigens will be studied by the production of monoclonal
anti-collagen antibodies, and collagen-reactive T-cell clones from CIA
susceptible and resistant mice. The relationship of genetic markers of
mouse CIA and human rheumatoid arthritis (RA) will be investigated by
cross-reactivity studies utilizing specific sera and cloned T-cells. Drug
studies using the CIA mouse model will investigate the genetic control of
drug responsiveness and toxic reactions during treatment of inflammatory
disease.
StatusFinished
Effective start/end date1/1/8312/31/85

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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