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Transforming growth factor β from multiple myeloma cells inhibits proliferation and IL‐2 responsiveness in T lymphocytes
Author(s) -
Cook Gordon,
Campbell John D. M.,
Carr Christine E.,
Boyd Kelly S.,
Franklin Ian M.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.6.981
Subject(s) - biology , multiple myeloma , transforming growth factor , growth factor , cancer research , immunology , microbiology and biotechnology , t lymphocyte , immune system , receptor , genetics
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 β1 (TGF‐β1). 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‐β inhibitor, TGF‐β latency‐associated peptide (LAP). MM cells suppressed IL‐2 responses but this inhibition was completely reversed by TGF‐β LAP. A CD25 − , IL‐2‐dependent blast cell line was not inhibited by MM cells or rhTGF‐β, 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‐β has a significant role to play. J. Leukoc. Biol. 66: 981–988; 1999.