Rats immunized with native but not denatured type II collagen (CII) intradermally develop a polyarthritis with histologic an radiographic manifestations resembling those found in patients with rheumatoid arthritis. This immunologically mediated model appears to be T cell dependent. To characterize the pathogenic and immunoregulatory mechanisms involved in the induction of collagen arthritis, rat T cell lines reactive to type II collagen have been established. Certain lines induce a synovitis when injected intraarticularly (I.A.), protect immunologically intact recipients from the induction of collagen arthritis when administered intravenously (I.V.), and produce an arthritogenic lymphokine. The proposed studies will develop a library of CII-reactive T cell clones from these lines and determine whether disparities in their bioactivity can be attributed to differences in antigen recognition, expression of a particular set of T cell antigen receptors, or arthritogenic lymphokine production. The CII clones will be screened with V gene probes to evaluate whether arthritogenicity is restricted to a limited repertoire of T cell receptors for type II collagen. Since only CII-reactive T cells appear to elaborate an arthritogenic lymphokine, additional experiments will identify the primary structure of this protein and define whether clonal arthritogenicity is inextricably linked to its generation. These studies should expand our understanding of T cell mediated processes in the pathogenesis of a chronic inflammatory synovitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR038844-04
Application #
3456838
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1988-07-15
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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