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

Multiple myeloma (MM) is a cancer of plasma cells, characterized by profound suppres- sion of host immune responses. Here we show that MM cell lines significantly suppress the prolifera- tion, blasting, response to interleukin-2 (IL-2), and expression of CD25 by concanavalin A (Con A)- activated or allostimulated peripheral blood T lym- phocytes. 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 b1 (TGF-b1). 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-b inhibitor, TGF-b latency-associated peptide (LAP). MM cells suppressed IL-2 responses but this inhibi- tion was completely reversed by TGF-b LAP. A CD25 2 , IL-2-dependent blast cell line was not inhibited by MM cells or rhTGF-b, 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 auto- crine IL-2/CD25 pathway and in response to IL-2, and that TGF-b has a significant role to play. J. Leukoc. Biol. 66: 981-988; 1999.