Transforming growth factor β 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 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 iu the G1 stage of the cell cycle, and do not enter time IL-2 autocrine growth pathway. T tell inhibition was mediated by a soluble factor. MM cell lines did not produce IL-10 but did produce large amounts of transforming growth factor beta 1 (TGF-beta 1). 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.