TY - JOUR
T1 - A regulatory system for soluble immune response suppressor production in steroid-responsive nephrotic syndrome
AU - Schnaper, H. William
N1 - Funding Information:
This study was presented in part at the 5th International Lymphokine Workshop, Clearwater, Florida, January, 1987 (Lymphokine Res 6: 1516A, 1987) and the Annual Meeting of the Society for Pediatric Research, Washington, D.C., May 1987 (Pediatr Res 2l:483A, 1987). This study was supported by Grant CA-40567 from the National Cancer Institute, NIH, and Grant number 2224 from the Council for Tobacco Research-USA, Inc., and a grant from the ESHE Fund. Dr. Schnaper is the recipient of Clinical Investigator Award DK01317 from the National Institute of Diabetes and Digestive and Kidney Diseases. April Wade, Robin Wesselschmidt and Susana Zahn provided invaluable technical assistance. We are grateful to Dr. Tim Ratliff, Jewish Hospital of St. Louis, for assaying fluids for IFN activity before and after absorption with anti-IFN sepharose, and to the laboratory of Dr. Robert Schreiber for performing ELISA for IFNy. Review of the manuscript by Dr. Carl Pierce was most helpful. Manuscript preparation by Jean Hankins, and the editorial assistance of Carole Shieber, are deeply appreciated.
PY - 1990/7
Y1 - 1990/7
N2 - 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 paients 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 healing to 56°C. This serum factor could be distinguished functionally and antigenically from SIRS and from interferon (IFN) α or IFNγ. 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.
AB - 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 paients 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 healing to 56°C. This serum factor could be distinguished functionally and antigenically from SIRS and from interferon (IFN) α or IFNγ. 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.
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U2 - 10.1038/ki.1990.180
DO - 10.1038/ki.1990.180
M3 - Article
C2 - 1696648
AN - SCOPUS:0025365155
VL - 38
SP - 151
EP - 159
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 1
ER -