Lack of normal CFU-C/suppressor activity in population of alloantigen-stimulated T cells from patients with chronic myelogenous leukemia.
Alloantigen-stimulated T cells from patients with Ph1-positive chronic myelogenous leukemia (CML) and normal individuals were obtained by one-way mixed lymphocyte cultures (MLC). Effects of alloantigen-stimulated T cells and MLC supernatants on colony formation were studied in vitro. Alloantigen-stimulated T cells were cocultured with normal allogeneic bone marrow cells (target cells) grown for CFU-C and BFU-E formation. Target cells were also cultured with MLC supernatants. Alloantigen-stimulated T cells from normal controls significantly suppressed CFU-C formation in the presence of human placental conditioned medium (HPCM), while those from CML patients failed to reduce it. MLC supernatants from CML patients were significantly less suppressive on CFU-C formation than those from normal controls. In contrast, not only normal and CML alloantigen-stimulated T cells but also their MLC supernatants increased BFU-E formation in a similar manner. Furthermore, MLC supernatants from normal controls as well as CML patients stimulated the growth of CFU-C from target cells in the absence of HPCM. These results suggest that CML T cells lack the ability to release soluble inhibitors of granulopoiesis, although the production of colony-stimulating factors and burst-promoting activities was equivalent to that of normal T cells after alloantigen stimulation in vitro. The failure of CML T cells to suppress granulopoiesis may contribute to the preferential proliferation of granulocytes in the pathophysiology of CML.
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D001772:Blood Cell Count; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D005260:Female; D006098:Granulocytes / Q000473:pathology*; D006410:Hematopoiesis; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000145:classification / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface