Co-expression of CD30 ligand and interleukin 4 (IL-4) receptors by acute myeloid leukaemia blasts is associated with the expansion of IL-4-producing CD30+ normal T cells (original) (raw)
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CD30L up-regulates CD30 and IL-4 expression by T cells
FEBS Letters, 2001
CD30L is frequently expressed on acute myeloid leukemia (AML) blasts. Its presence is associated with the coexpression of interleukin-4 (IL-4) receptor and with the expansion of specific T-helper 2 (Th2) cell subsets producing IL-4 and expressing CD30. Recombinant CD30L-bearing cells up-regulated the expression of surface CD30 and increased the production of IL-4 and soluble (s) CD30 by co-cultured T cells. These findings were confirmed with AML blasts expressing surface CD30L, where blocking anti-CD30 antibodies completely abolished the release of sCD30 and reduced the production of IL-4. Our data indicates a direct role of CD30L + neoplastic cells in driving the immune response toward a Th2-polarized nonprotective state. ß 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
British Journal of Haematology, 1999
Phenotypic and functional abnormalities within the residual non-B-cell compartment of B-cell chronic lymphocytic leukaemia (CLL) suggest an interaction between tumour cells and host immune effectors. To explore the possibility of a polarized Th1/Th2 response we have studied CD30 antigen expression and the pattern of cytokine production by purified CLL T cells. Activated T cells from CLL patients showed a significant increase in the expression of CD30 compared to normal controls. Accordingly, high levels of soluble CD30 were detected in supernatants from activated T-cell cultures, as well as in CLL serum samples. Messenger RNA for IL4 was found in both resting and, to a greater extent, in activated CLL T lymphocytes. The latter cells were also capable of releasing IL4. Three-colour immunofluorescence analyses revealed a strong CD30 expression in the CD3 þ /CD8 þ /CD28 ¹ large granular lymphocyte subset, which is considerably expanded in CLL. Production of IL4, as well as expression and release of CD30 by these T cells, was conclusively demonstrated at the clonal level. These findings document an expansion of a peculiar subset of 'Th2-like' cells in CLL, with an increased IL4 production and CD30 expression and release, that are likely to contribute to both the B-cell accumulation and immunedefects characteristic of this disease.
Annals of clinical and laboratory science
The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-g (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 ± 1056) and lowest in the dysplastic AML group (960 ± 545). The IFN-g level was highest in the acute promyelocytic leukemia (APL) group (495 ± 159), and lowest in the ALL group (252 ± 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 ± 1049) and lowest in the APL group (397 ± 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-g are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.
Preferential expression of CD30 by human CD4+ T cells producing Th2-type cytokines
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1995
A large panel of human CD4+ T helper (Th) cell clones with established Th1, Th2, or Th0 profiles of cytokine secretion were examined for the expression of CD30, a member of the tumor necrosis factor receptor superfamily. Th1 clones expressed poor or no CD30 mRNA, and showed low or undetectable expression of both membrane and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and membrane CD30 and released substantial amounts of sCD30. Th0 clones exhibited an intermediate pattern of CD30 expression and release. When T cells from the same donor were stimulated with three different antigens (purified protein derivative, PPD; Toxocara canis excretory/secretory antigen, TES; Lolium perenne group I, Lol p I), production of high concentrations of IFN-gamma, but not expression of CD30 or production of IL-4 and IL-5, were observed at any time after stimulation with PPD. In contrast, both CD30 expression and production of IL-4 and IL-5, but not of IFN-gamma, were concomita...
Cell Communication & Adhesion, 2016
To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n ¼ 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-a, interferon-c) in supernatants of mixed-lymphocyte-culture and in serum (n ¼ 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.
Annals of Clinical and Laboratory Science, 2006
The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-g (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 ± 1056) and lowest in the dysplastic AML group (960 ± 545). The IFN-g level was highest in the acute promyelocytic leukemia (APL) group (495 ± 159), and lowest in the ALL group (252 ± 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 ± 1049) and lowest in the APL group (397 ± 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-g are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.