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.
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.
D002455:Cell Division; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D010455:Peptides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors