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Induction of synthesis of the cytolytic C9 (ninth component of complement)-related protein in human peripheral mononuclear cells by monoclonal antibody OKT3 or interleukin 2: correlation with cytotoxicity and lymphocyte phenotype

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
Synthesis of the cytolytic C9-related protein (C9RP) was induced by activation of resting human peripheral T lymphocytes with the anti-CD3 antibody OKT3 or interleukin 2. Comparison of cellular cytotoxicity and C9RP content at various times during activation yielded a coefficient of correlation r = 0.92. During OKT3 stimulation of peripheral mononuclear cells, maximal C9RP content and cytotoxicity were observed by day 2 for 3, with subsequent decline to baseline values by day 5, whereas during interleukin 2 stimulation, both parameters reached the maximal level at days 3-5. After fluorescence-activated cell sorting, C9RP and cytotoxicity were quantitated in CD4/sup +/, CD8/sup +/, and Leu-19/sup +/ subsets. In OKT3-activated CD8/sup +/ cells, C9RP increased to approx. 3 x 10/sup 6/ molecules per cell, with a corresponding increase in lysis of human melanoma cells mediated by anti-CD3-anti-melanoma monoclonal antibody conjugates. Interleukin 2-stimulated CD8/sup +/ cell showed similar increases, but cytotoxicity was conjugate-independent. Activated CD4/sup +/ cells showed minimal increase in C9RP content. Leu-19/sup +/ cells, which exhibit natural killer cell activity, had a high C9RP content before stimulation.
Research Organization:
Research Institute of Scripps Clinic, La Jolla, CA
OSTI ID:
5964246
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:9; ISSN PNASA
Country of Publication:
United States
Language:
English