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The Journal of Immunology, 1976, 116: 1140-1144.
Copyright © 1976 by The American Association of Immunologists, Inc.

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Regulatory Substances Produced by Lymphocytes

III. Evidence That Lymphotoxin and Proliferation Inhibitory Factor Are Identical and Different from the Inhibitor of DNA Synthesis1

Yuziro Namba2 and Byron H. Waksman

From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510

Abstract

L cell mutant lines which were considerably more resistant to rat lymphotoxin (LT) than the original cell line were obtained by periodic additions of LT, partially purified from sensitized lymph node cell culture supernatants by DEAE-cellulose chromatography and Sephadex gel filtration. Addition of actinomycin D to cultures of these mutant cells abrogated resistance to LT, suggesting that resistance was not due to a loss of LT receptors but probably to increased activity of a repair mechanism. These mutant lines were also more resistant to the proliferation inhibitory effect of LT in low concentration and to that of diluted culture supernatants of lymph node cells stimulated with antigen (ovalbumin) than the original cell line, but they remained as sensitive to inhibitor of DNA synthesis (IDS) as the original line. The mutant lines also remained fully sensitive to both complement-dependent lysis by antibody and antibody-dependent cellular cytotoxicity, but showed increased resistance to the killing effect of rat lymph node cells sensitized with original L cells in vivo. These findings suggest that the lymphotoxic substance partially purified and characterized in this and in the previous paper may be an important mediator of T cell-mediated cytotoxicity.

Footnotes

1 This work was supported by United States Public Health Service Research Grants AI-06112, AI-06455, and Contract CB-43926.

2 On leave of absence from the Department of Pathology, Institute for Virus Research, Kyoto University, Kyoto, Japan.







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