Affiliation:
1. Department of Immunology, United Medical and Dental Schools of Guy's and St Thomas' Hospitals, Guy's Hospital, London, England
2. Department of Rheumatology, London Hospital Medical College, London, England
Abstract
SUMMARY
Autoimmunity may be due to augmentation of immune responses by human CD8 cells which bind the lectin Vicia villosa (VV). We have investigated T cells in rheumatoid arthritis (RA) by double immunofluorescence flow cytometry, in order to assess VV-binding CD8 and CD4 cells from the peripheral blood and synovial fluid. A significant increase in CD8+ VV adherent (P<0.0001) and CD4+ VV adherent cells (P <0.001) was found in synovial fluid, as compared with peripheral blood from patients with RA. A significant increase in VV-binding CD8+ or CD4+ cells was, however, not found in the blood of patients with RA, as compared with controls. We suggest that the lack of VV-binding T cells separated from blood, in contrast to those from synovial fluid, may be due to an inhibiting agent expressing N-acetyl d-galactosamine. Indeed, IgA1 is rich in N-acetyl d-galactosamine, it inhibits VV binding to T cells and is significantly bound to CD8 cells (P<0.001). The IgA1 was then characterized and in about half the patients J chains and secretory component was found, suggesting that the IgA1 is of the polymeric and secretory variety. IgA bound to the T cells engaged the Fcα receptors and a significant decrease in the Fcα receptors was found in CD8 cells (P<0.000l) and CD4 cells (P<0.0l). Desorption studies were then carried out on CD8 and CD4 cells which showed that a loss of cell-bound IgA1 was associated with an increase in VV binding. Conversely, adsorption of IgA to T cells was associated with a loss in VV binding. The results suggest that the failure of VV binding to CD8+ andCD4+ cells from peripheral blood of patients with RA can be ascribed to cell-bound IgA 1. Cytophilic IgA1 may inhibit the function of CD8+ VV binding cells, thereby preventing augmentation of the systemic immune response, consistent with the lack of extra-articular disease in these patients with RA.
Publisher
Oxford University Press (OUP)
Subject
Immunology,Immunology and Allergy
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