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 cytotoxic activity are impaired at time of diagnosis due to not-yet-identified soluble immunosuppressing factors. The inhibition of autologous antileukemic immune response by these factors may support immunosurveillance 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 cytotoxic activity in AML at time of diagnosis, we looked for the TGF-beta 1-specific mRNA, for the production and release of TGF-beta 1, and for its relevance for immunosuppressing activities in AML. In the culture supernatants of 18 investigated AMLs, we detected various amounts of TGF-beta protein. The TGF-beta 1 and TGF-beta 2 protein concentrations were 105 pg/mL (< 50-240 pg/mL) and 32 pg/mL (< 2-91 pg/mL), respectively. In 13 of 15 patients, the leukemic blasts expressed TGF-beta 1 mRNA. To exclude possible interferences with contaminating mononuclear cells (MNC), the data were confirmed by analysis of sorted blast cells and leukemic cell lines. All investigated leukemic cell lines expressed TGF-beta 1 protein and mRNA. The culture supernatants of AMLs inhibited LAK activity strongly in a dose-dependent manner. The inhibition of cytotoxicity could be restored by the addition of neutralizing TGF-beta 1 antibodies. The data suggest TGF-beta 1 to be a relevant factor for the inhibition of cytotoxic activities in AMLs.
Medical Clinic III, J.W. Goethe University, Frankfurt/Main, Germany.
L
L
Bergmann
D K
DK
Schui
J
J
Brieger
E
E
Weidmann
P S
PS
Mitrou
D
D
Hoelzer
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D005260:Female; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta