THE INHIBITION OF LYMPHOKINE-ACTIVATED KILLER-CELLS IN ACUTE MYELOBLASTIC-LEUKEMIA IS MEDIATED BY TRANSFORMING GROWTH FACTOR-BETA(1)

In acute myeloblastic leukemia (AML), the T cell response and cytotoxi c activity are impaired at time of diagnosis due to not-yet-identified soluble immunosuppressing factors. The inhibition of autologous antil eukemic immune response by these factors may support immunosurveillanc e of AML. A well-known inhibitor of lymphokine-activated killer (LAK) cell activity is transforming growth factor-beta(1) (TGF-beta(1)). To evaluate the possible significance of TGF-beta(1) for the impaired cyt otoxic activity in AML at time of diagnosis, we looked for the TGF-bet a(1)-specific mRNA, for the production and release of TGF-beta(1), and for its relevance for immunosuppressing activities in AML. Tn the cul ture supernatants of 18 investigated AMLs, we detected various amounts of TGF-beta protein. The TGF-beta(1) and TGF-beta(2) protein concentr ations were 105 pg/mL (<50-240 pg/mL) and 32 pg/mL (<2-91 pg/mL), resp ectively. In 13 of 15 patients, the leukemic blasts expressed TGF-beta (1) mRNA. To exclude possible interferences with contaminating mononuc lear cells (MNC), the data were confirmed by analysis of sorted blast cells and leukemic cell lines. All investigated leukemic cell lines ex pressed TGF-beta(1) protein and mRNA. The culture supernatants of AMLs inhibited LAK activity strongly in a dose-dependent manner. The inhib ition of cytotoxicity could be restored by the addition of neutralizin g TGF-beta(1) antibodies. The data suggest TGF-beta(1) to be a relevan t factor for the inhibition of cytotoxic activities in AMLs.