Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes

J Leukoc Biol. 1999 Dec;66(6):981-8. doi: 10.1002/jlb.66.6.981.


Multiple myeloma (MM) is a cancer of plasma cells, characterized by profound suppression of host immune responses. Here we show that MM cell lines significantly suppress the proliferation, blasting, response to interleukin-2 (IL-2), and expression of CD25 by concanavalin A (Con A)-activated or allostimulated peripheral blood T lymphocytes. T cells arrest in the G1 stage of the cell cycle, and do not enter the IL-2 autocrine growth pathway. T cell inhibition was mediated by a soluble factor. MM cell lines did not produce IL-10 but did produce large amounts of transforming growth factor beta1 (TGF-beta1). T cells were assessed for their ability to respond to IL-2 when co-cultured with MM cells in the presence or absence of the TGF-beta inhibitor, TGF-beta latency-associated peptide (LAP). MM cells suppressed IL-2 responses but this inhibition was completely reversed by TGF-beta LAP. A CD25-, IL-2-dependent blast cell line was not inhibited by MM cells or rhTGF-beta, confirming the specificity of the inhibition mechanism for the IL-2 autocrine growth pathway. We conclude that MM cells suppress T cells in their entry into the autocrine IL-2/CD25 pathway and in response to IL-2, and that TGF-beta has a significant role to play.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / antagonists & inhibitors*
  • Adjuvants, Immunologic / physiology
  • Apoptosis / immunology
  • Cell Communication / immunology
  • Cell Cycle / immunology
  • Coculture Techniques
  • Concanavalin A / antagonists & inhibitors
  • Humans
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-2 / physiology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Lymphocyte Culture Test, Mixed
  • Mitogens / antagonists & inhibitors
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Peptide Fragments*
  • Protein Precursors*
  • Proteins / pharmacology
  • Receptors, Interleukin-2 / biosynthesis
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured


  • Adjuvants, Immunologic
  • Interleukin-2
  • Mitogens
  • Peptide Fragments
  • Protein Precursors
  • Proteins
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Concanavalin A