Monocyte involvement in PHA induced cytotoxicity of chicken erythrocytes in man.
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Biomedical subjects
Publications and source records attributed to M A Scheinberg.
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Seven patients with diffuse proliferative lupus nephritis were subjected to highdose intravenous methylprednisolone (pulse) therapy. Following the pulse, five patients with rapidly deteriorating ranal function improved within three days and their serum-creatinine levels returned to baseline by one month. All seven patients demonstrated reversal of severe immunological abnormalities including increased serum D.N.A binding, decreased serum C3 levels, and reduced number of T lymphocytes in the peripheral blood. This form of therapy may make it possible to maintain patients with lupus nephritis on lower doses of steroids than is normally feasible.
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Evidence is presented that T cell impairment appears to be specifically related to the pathogenesis of experimental amyloidosis. This conclusion is based on the finding that thymosin administration improves T cell function as measured by mitogen stimulation of spleen cell suspension and at the same time reduces the incidence and severity of amyloid disease in casein-treated mice.
Antibody-dependent direct cytotoxicity (ADDC) is generally believed to be unrelated to T-cell function in experimental animals. The role of ADDC in humans and its clinical usefulesss was evaluated in patients with systemic lupus erythematosus (SLE) and normal controls. Peripheral blood lymphocytes from patients with active SLE were unable to lyse antibody-coated target cells in vitro to the same degree as lymphocytes from patients with inactive SLE and controls. Sera from patients with active SLE suppressed ADDC by lymphocytes derived from normal controls and this abnormality was not corrected by overnight incubation or by extensive washing of lymphocyte preparations. Although there was poor correlation between ADDC and the proportions of B cells and null cells in effector lymphocyte populations from SLE patients and controls, it is concluded that this assay provides another means of determining immune competence in man.
Antibody-dependent direct cytotoxicity (ADDC) by human lymphocytes was evaluated in patients with rheumatoid arthritis and normal controls. Purified peripheral blood and synovial fluid lymphocytes mediated normal ADDC when compared to control subjects. No correlation could be obtained between the percentages of T, B and null cells in effector cell populations and the degree of 51Cr released from target cells. Sera from 50% of patients with rheumatoid arthritis inhibited ADDC by normal lymphocytes; the degree of inhibition did not correlate with the titre of IgM rheumatoid factor. The pathogenic implications of these findings are discussed.
A high incidence of spontaneous amyloidosis is described in SJL/J mice. Amyloid was detected as early as 30 weeks of age and the incidence rose to 90 per cent by 60 weeks of age. Amyloid deposits were most prominent in the perifollicular zones of the spleen and the lobular areas of the liver. Ultrastructural analysis revealed rigid, nonbranching fibrils indistinguishable from those observed in casein-induced murine amyloidosis. On the other hand, immunochemical studies indicated that amyloid deposits in SJL/J mice differ from those found in casein-treated CBA mice with respect to size, amino acid content, and antigenic properties. Since the SJL/J mouse also develops spontaneous reticulum cell tumors and serum M components, it appears to be a useful model for study of the pathogenesis of amyloidosis and its relationship to aging, neoplasia, and certain B-cell dyscrasias.
The relationship between cellular (B-cell) responses and the development of casein-induced amyloidosis was explored. The main findings are: (1) B-cell abnormalities are more pronounced in amyloid susceptible CBA/J than in amyloid resistant A/J mice; these include increased mitogen responses to SIII, PI:C and DXS, and enhanced primary immune responses to T-independent antigens; (2) CBA/J amyloid spleen cell suspensions appear to be enriched with antibody dependent killer cells and precursors of antibody-forming cells; these abnormalities are not seen in casein treated A/J mice. This hitherto unrecognized proliferation of immunoblasts in casein-treated CBA/J animals raises the possibility that B cell-macrophage interaction may play an important role in the pathogenesis of amyloid disease.
Although thymosin, a thymic hormone, has been shown to restore cellular immunity in NZB/NZW mice, its effect in human systemic lupus erythematosus (S.L.E.) and other auto-immune disorders has not been tested. The present study shows for the first time that the proportion of "null cells" in peripheral-blood lymphocytes of patients with active S.L.E. is significantly decreased after in-vitro thymosin treatment. Thymosin has no effect on the percentages of T cells, B cells, and "null" cells in peripheral-blood lymphocytes from normal controls and patients with inactive S.L.E. and active rheumatoid arthritis. These findings suggest that thymosin may play an important part in the pathogenesis and treatment of this condition.
Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.
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Serum immunoglobulin abnromalities in nonfamilial and systemic primary amyloidosis are distinct from those seen in multiple myeloma and more closely resemble those seen in benign monoclonal gammopathy. Surface lymphocyte characteristics also differentiate amyloid patients with or without monoclonal immunoglobulins from those with malignant B-cell dyscrasias. In vitro lymphocyte transformation with phytohemagglutinin and pokeweed mitogen is normal in amyloidosis, but T-cell function is significantly depressed in both primary and secondary amyloid disease as measured by concanavalin A responses.