Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors.
Progressive growth of metastatic Lewis lung carcinoma (LLC-LN7) tumors is associated with increased levels of bone-marrow-derived CD34+ cells having natural suppressor (NS) activity toward T cells. The present studies determined whether tumor-derived products are responsible for this induction of NS activity. Culturing normal bone marrow cells with LLC-LN7-conditioned medium (LLC-CM) or with recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) resulted in the appearance of NS activity. The development of NS activity coincided with a prominent increase in the levels of CD34+ cells. That the CD34+ cells were responsible for the NS activity of the bone marrow cultures containing LLC-CM was shown by the loss of NS activity when CD34+ cells were depleted. The stimulation of CD34+ NS cells by LLC-CM was attributed to tumor production of GM-CSF, since neutralization of GM-CSF within the LLC-CM reduced its capacity to increase CD34+ cell levels. Studies also showed that the induction of CD34+ NS cells by LLC-CM and GM-CSF could be overcome by including in the cultures an inducer of myeloid differentiation, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These results demonstrate that the mechanism by which the LLC-LN7 tumors stimulate increased levels of CD34+ NS cells from normal bone marrow is by their production of GM-CSF and that this can be blocked with the myeloid differentiation inducer 1,25(OH)2D3.
Research Service, Hines VA Hospital, IL 60141, USA.
M A
MA
Wright
K
K
Wiers
K
K
Vellody
D
D
Djordjevic
M R
MR
Young
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology*; D002117:Calcitriol / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol