T cells appear to play a role in the pathogenesis of rheumatoid arthritis although there has been no demonstration of T cell reactivity to putative disease-related antigens. Recent advances in the understanding of the structure and genetics of the T cell antigen-receptor have made available new approaches to the study of T cell specificity. In this proposal T cell clones will be derived from the synovial space (SS) of a well defined subset of RA patients, i.e. classical or definite RA with proliferative synovitis. The disease-specific T cell clones will be identified from among the heterogeneous clones derived from this site of inflammation on the basis of finding a clonal or oligoclonal distribution of antigen receptor gene rearrangements. T cells derived from the SS of patients with Lyme arthritis will be similarly studied as a model in which the disease related antigen is known. Interleukin-2 dependent T cell clones from the SS and the peripheral blood will be derived from patients with Lyme arthritis and RA. In the case of Lyme arthritis, T cell clones will be grown with the causative agent, B. burgdorferi. In addition, T cell clones will be grown in parallel with anti-T3 antibody to further confirm that anti-T3 antibody can maintain the antigen- specificity of T cell lines grown in the absence of specific antigens. In the case of RA, T cell clones will be grown only with anti-T3 antibody. T cell receptor rearrangements utilized by these T cell clones will be studied by using Southern blot analysis (including pulse-field electrophoresis for the alpha chain) and DNA sequencing. The long-term goal of the present proposal is to identify the disease-specific T cells derived from the synovial space in RA and generate monoclonal antibodies directed toward the T cell receptor on such cells. Such antibodies would be of theoretical, diagnostic, and perhaps therapeutic significance.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
Application #
Study Section
Immunological Sciences Study Section (IMS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Connecticut
Schools of Medicine
United States
Zip Code
Gerber, M A; Shapiro, E D; Bell, G L et al. (1995) Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease. J Infect Dis 171:724-7
Padula, S J; Sampieri, A (1995) T-cell receptor use in early rheumatoid arthritis. Ann N Y Acad Sci 756:147-58
Padula, S J; Dias, F; Sampieri, A et al. (1994) Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease. J Clin Microbiol 32:1733-8
Padula, S J; Broketa, G; Sampieri, A et al. (1994) Increased collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy. Evidence for trans-activational regulation of collagen transcription. Arthritis Rheum 37:1386-94
Padula, S J; Sampieri, A; Dias, F et al. (1993) Molecular characterization and expression of p23 (OspC) from a North American strain of Borrelia burgdorferi. Infect Immun 61:5097-105
Padula, S J; Lingenheld, E G; Stabach, P R et al. (1991) Identification of encephalitogenic V beta-4-bearing T cells in SJL mice. Further evidence for the V region disease hypothesis? J Immunol 146:879-83
Ruddle, N H; Bergman, C M; McGrath, K M et al. (1990) An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med 172:1193-200
Love Jr, J T; Padula, S J; Lingenheld, E G et al. (1989) Effects of H-7 are not exclusively mediated through protein kinase C or the cyclic nucleotide-dependent kinases. Biochem Biophys Res Commun 162:138-43
Wong, R L; Ruddle, N H; Padula, S J et al. (1988) Subtypes of helper cells. Non-inflammatory type 1 helper T cells. J Immunol 141:3329-34