Rheumatoid synovial effusions (and other inflammatory joint fluids are characterized by large numbers of T cells, many of which are activated, and another ill-defined population lacking cell surface receptors (E negative, Ig negative, Fc negative). Little is known about the functional significance of either population. There is evidence, however, for natural killer cell activity mediated by an Fc receptor negative NK cell. These characteristics are reminiscent of the results of the in vitro autologous mixed leukocyte reaction. We propose to analyze the following hypothesis; namely, in the rheumatoid joint B lymphocytes, transformed by an undefined stimulus, generate an autologous MLR. This leads to activation of T cells and the elaboration of factors that augment nonspecific cytotoxic activity. An additional consequence of this reaction would be the generation of large amounts of nonspecific T cell-derived helper activity. This thesis would predict that in the rheumatoid joint one would find evidence of an increased or secondary type of autologous MLR, an unusual population of AMLR stimulator cells, the presence of nonspecific cytotoxic cells lacking Fc receptors, and perhaps specific cytotoxic cells recognizing lymphocyte membrane defined antigen induced by the B cell transforming agent.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR014916-16
Application #
3154820
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1976-05-01
Project End
1989-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
16
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Alvaro-Gracia, J M; Zvaifler, N J; Firestein, G S (1989) Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. J Exp Med 170:865-75
Bergroth, V; Tsai, V; Zvaifler, N J (1989) Differences in responses of normal and rheumatoid arthritis peripheral blood T cells to synovial fluid and peripheral blood dendritic cells in allogeneic mixed leukocyte reactions. Arthritis Rheum 32:1381-9
Tsai, V; Bergroth, V; Zvaifler, N J (1989) Dendritic cells in health and disease. J Autoimmun 2 Suppl:33-43
Firestein, G S; Xu, W D; Townsend, K et al. (1988) Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med 168:1573-86

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