B- and T-lymphocytes in rheumatoid synovitis and the effect of cyclophosphamide.
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Biomedical subjects
Publications and source records attributed to E R Hurd.
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In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of (125)I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.
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The mechanism of action of 6-mercaptopurine (6-MP) on an egg albumin-induced inflammatory lesion in the skin has been studied in rabbits treated with 6-MP in a daily dosage of 18 mg/kg. Relative to control animals, significant decreases in the numbers of large lymphocytes and monocytes in the blood were observed in the 6-MP-treated animals by the 9th day of treatment, without significant decrease in the numbers of polymorphonuclear leukocytes and small and medium lymphocytes. Concurrently, a significant decrease was also seen in the percentage of tissue mononuclear cells in the inflammatory skin lesion. There was a highly significant correlation between the numbers of monocytes in the blood and the per cent of mononuclear cells in the lesion. A mean of 52% of the mononuclear cells in the tissue lesion phagocytosed carbon offering further evidence that the major cell involved was the blood monocyte. In vitro incorporation of (3)H-Tdr by blood mononuclear cells was significantly reduced in the 6-MP-treated animals as determined by scintillation counting and radioautography. The large lymphocyte was the predominant cell type which was labeled in vitro. Small lymphocytes and monocytes were rarely labeled. The data obtained suggest that the anti-inflammatory effect of 6-MP, reflected in these experiments by a decrease in mononuclear cells in a tissue lesion, results from suppression of a bone marrow response to local inflammation, affecting principally proliferating precursors of blood monocytes and large lymphocytes. The possible importance of this action of 6-MP in the treatment of inflammatory and immunologically mediated disease is discussed.
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Absolute numbers of B (IgG-, IgM-, and IgA-staining) and T lymphocytes (sheep erythrocyte rosette-forming cells) were determined in patients with systemic lupus erythematosus and other connective tissue diseases in cyclophosphamide-treated and noncyclophosphamide-treated patients and in control subjects. In patients receiving cyclophosphamide, all three types of immunoglobulin-staining varieties of circulating B lymphocytes were significantly decreased. At the same time the circulating T lymphocytes were also significantly reduced. In patients with scleroderma treated with therapeutic doses of cyclophosphamide and studied sequentially, the reduction in B lymphocytes occurred first, with eventual depletion of both cell types. In 2 patients, an early rebound increase in T cells occurred followed by a marked reduction. These data indicate that the immunosuppressive effects of cyclophosphamide may be associated with a reduction in both cell types.