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American Journal of Pathology, Vol 131, 569-577, Copyright © 1988 by American Society for Investigative Pathology


REGULAR ARTICLES

Production of transforming growth factor-beta activity by Ki-1 positive lymphoma cells and analysis of its role in the regulation of Ki-1 positive lymphoma growth

SR Newcom, ME Kadin and AA Ansari
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

The growth of activated human T lymphocytes in response to interleukin- 2 (IL-2) is suppressed by transforming growth factor-beta (TGF-beta). This study presents data that show a diminished response of two human lymphoma cell lines to physiologic regulation by TGF-beta. Cell line L- 428 was derived from the malignant pleural effusion of a patient with far advanced nodular sclerosing Hodgkin's disease and has been shown to have clonal gene rearrangements characteristic of both B and T lymphocytes. Cell line Mac-1 was derived from the blood of a patient with clinically indolent cutaneous T-cell lymphoma. Both cell lines express the Hodgkin's disease associated antigen, Ki-1. These Ki-1 positive lymphomas are shown to secrete TGF-beta into serum-free culture media. The addition of picogram quantities of exogenous TGF- beta to cell cultures of indolent Ki-1 lymphoma (Mac-1) suppresses IL-2- dependent mitosis; however, the suppression is less than 45%. This suppression correlates with a decrease in the number of IL-2 receptors. No inhibition of Ki-1 positive Hodgkin's cells (L-428) was observed, and proliferation dependent on polyclonal IL-2 was either not affected or was slightly potentiated by TGF-beta. Receptor analysis indicates the absence of IL-2 and TGF-beta receptors on L-428 cells. Thus, these Ki-1 lymphomas derived from activated lymphocytes appear to secrete TGF- beta activity but continue to proliferate because of defective suppression of IL-2 (and related lymphokine)-dependent DNA synthesis.


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Copyright © 1988 by the American Society for Investigative Pathology.