A regulatory system for soluble immune response suppressor production in steroid-responsive nephrotic syndrome.
Patients with nephrotic syndrome frequently have suppressed immune responses. Previously, it has been determined that subjects with steroid-responsive nephrotic syndrome (SRNS) produce the lymphokine, soluble immune response suppressor (SIRS). In the present group of experiments, a potential pathway of suppressor cell activation was investigated. Sera from patients with SRNS stimulated normal CD8+ lymphocytes to produce SIRS. Serum SIRS-inducing activity was abrogated by treatment with proteinase K or boiling, but was not affected by dialysis, acidification to pH 2, or heating to 56 degrees C. This serum factor could be distinguished functionally and antigenically from SIRS and from interferon (IFN) alpha or IFN gamma. Supernatants of cultured patient lymphocytes enriched for CD4+ cells were also found to activate normal CD8+ lymphocytes to produce SIRS. The lymphocyte-derived activity showed similar characteristics to those of the serum factor. Molecular weight of both factors was estimated to be 13,000 to 18,000 daltons by gel filtration chromatography, and activity of serum and lymphocyte supernatant from the same patients eluted with similar patterns on reversed-phase HPLC. These data suggest that serum SIRS-inducing activity is derived from a suppressor-inducer lymphocyte, and indicate the presence of a regulatory mechanism for SIRS production in steroid-responsive nephrotic patients.
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
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Schnaper
D002648:Child; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007372:Interferons / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis*; D009402:Nephrosis, Lipoid / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor; D007372:Interferons