CD30L up-regulates CD30 and IL-4 expression by T cells (original) (raw)
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British Journal of Haematology, 2002
CD30 ligand (CD30L), but not its cognate receptor CD30, is frequently expressed on acute myeloid leukaemia (AML) blasts. In the present study, we found that leukaemic blasts presenting surface CD30L displayed a characteristic cytokine-receptor pattern that makes them ideal targets for those cytokines usually produced by Th2-type cell subsets. In particular, even though a broad distribution of Th2 cytokine receptors by AML blasts was shown, we demonstrated the almost exclusive expression of interleukin 4 (IL-4) receptor (R), in the absence of its cognate cytokine, by CD30L + AML. Furthermore, a number of Th2-associated markers, including CD30, IL-4 and GATA-3, were expressed by residual T cells derived from CD30L + AML but not from CD30L -AML, in which the presence of the Th1-associated marker LAG-3 was doc-umented in some cases. The production of IL-4 in the absence of interferon c (IFN-c) was also detected in CD3 + / CD30 + T cells from CD30L + AML. These results, along with the shift toward IL-4-producing specific T-cell clones observed in CD30L + AML samples by enzyme-linked Immunospot (ELISpot) assay, were consistent with the hypothesis of a Th2 polarization taking place in T cells from CD30L + AML. The notion that IL-4 was able to enhance in vitro proliferation of CD30L + /IL-4R + purified leukaemic blasts suggests that the selective interaction of IL-4-producing CD30 + T cells with CD30L + leukaemic progenitors may have a role in the progression of this particular AML subset.
Journal of Clinical & Cellular Immunology, 2017
Objectives: As we noted that CD30 is a valuable molecule in regulation of growth and death of lymphocytes in malignant lymphomas, we analyzed CD30 expression and serum soluble CD30 (sCD30) molecule level in patients with acute myeloid leukemia (AML) to assess their role as a prognostic markers and to examine the possibility of anti-CD30 to be a targeted therapy in these patients. Methods: We studied CD30 expression by Multicolor flow cytometry immunophenotypic analysis on bone marrow aspirates of 50 AML patients. Serum sCD30 level was measured by Enzyme Linked Immunosrbent Assay (ELSA). We correlate CD30 and sCD30 values with all of white blood cell counts, Hemoglobin, platelets, bone marrow blasts and cytogenetics. The Fisher's exact test or chi-square was used for comparison of categorical variables and the ttest or one-way analysis of variance (ANOVA) was applied for numerical comparisons using SPSS version 20. A p value of <0.05 was considered to be statistically significant. Results: Our study conducted on 50 AML patients, the mean patients' age was 47.4 ± 18.1 years (range, 17-77), 11 (22%) were males and 39 (78%) were females. 16 (32%) patients have high CD30-expression and 11 (22%) have elevated serum sCD30. We found that there was a significant correlation between both CD30 expression and sCD30 level with WBCs count, BM blasts, Adverse risk cytogenetics, FLT3/ITD and with relapse for CD30 expression, complete remission failure with elevated serum sCD30 level. Conclusions: CD30 is expressed by myeloblasts in AML patients. We found that high CD30 expression and elevated sCD30 level can be used as prognostic markers for relapse and complete remission failure respectively. Furthermore, these patients with adverse risk cytogenetics have not too many treatment options, so the use anti-CD30 targeted therapy may be a possible alternative for this patient group which need further studies.
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...
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.
CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues
PubMed, 1996
The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.
Frequent Expression of the Variant CD30 in Human Malignant Myeloid and Lymphoid Neoplasms
The American Journal of Pathology, 1999
We earlier identified a variant of CD30 (CD30v) that retains only the cytoplasmic region of the authentic CD30. This variant is expressed in alveolar macrophages. CD30v can activate the nuclear factor-B (NF-B) as CD30 , and its overexpression in HL-60 induced a differentiated phenotype. To better understand the physiological and pathological functions of CD30v, expression of this variant was examined using a multiple approach to examine 238 samples of human malignant myeloid and lymphoid neoplasms. Screening by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of CD30v transcripts in 52 of 72 , 7 of 11 , 63 of 90 , and 7 of 30 samples of acute myeloid leukemia (AML) , myeloid blast crisis of myeloproliferative disorders (MBC), and lymphoproliferative disorders (LPDs) of B-and T-cell origin , respectively. CD30v expression was high in monocyte-oriented AMLs (FAB M4 and M5), B-cell chronic lymphocytic leukemia (B-CLL), and multiple myeloma (MM). Using the specific antibody HCD30C2 , prepared using a peptide corresponding to the nine amino acids of the amino-terminal CD30v, expression of CD30v protein was detected in 10 of 25 and 2 of 10 AML and ALL samples , respectively. In AMLs , immunocytochemical detection of CD30v revealed the presence of loose clusters of CD30v-expressing cells dispersed amid a population of CD30vnegative blasts. Finally , the parallel expression of CD30v mRNA and protein , as evidenced by Northern and Western blotting , was confirmed in selected cases of AMLs and LPDs. A significant correlation was found between expressions of CD30v and CD30 ligand transcripts in AML and LPD (P ؍ 0.02, odds ratio ؍ 3.2). The association of CD30v with signal-transducing proteins, tumor necrosis factor receptor-associated factor (TRAF) 2, and TRAF5 was demonstrated by coimmunoprecipitation analysis, as was demonstrated for authentic CD30 protein. Expression of transcripts for TRAF1, TRAF2, TRAF3, and TRAF5, as demonstrated by RT-PCR, was noted in leukemic blasts that express CD30v. Collectively, frequent expression of CD30v along with TRAF proteins in human neoplastic cells of myeloid and lymphoid origin provide supportive evidence for biological and possible pathological functions of this protein in the growth and differentiation of a variety of myeloid and lymphoid cells. (Am J Pathol 1999, 155:2029 -2041)
CD30 ligand is expressed on resting normal and malignant human B lymphocytes
British Journal of Haematology, 1996
CD30, a member of the tumour necrosis receptor superfamily, is physiologically expressed on a subpopulationof T helper cells in normal individuals but is also expressed on several malignant and virally transformed cells. Its ligand (CD30L) is a pleiotropic cellular transmembrane protein that can induce cell death in several CD30 cell lines. CD30L expression has been reported on activated human peripheral blood T lymphocytes and macrophages but not on B cells. Here we show that the CD30L is expressed on resting normal and on malignant B cells in addition to both CD4 and CD8 subsets of activated T cells, making it the second tumour necrosis family member, in addition to the CD27 ligand, that can be expressed on both T and B cells. These findings raise the possibility that the CD30L has a role in B-cell/T-cell communication and that B and T cells are likely to be involved in the growth regulation of CD30 tumours.
Blood, 1997
CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hair...
Engagement of CD30 shapes the secretion of cytokines by human ??d T cells
Eur J Immunol, 2000
CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human +ˇT cells. Elevated surface levels of this molecule persisted in long-term cultures of +ˇcells, without further cell stimulation. CD30 acted as a co-stimulus in +ˇT cells by potentiating the intracellular Ca 2+ fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-+ but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1 g were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by +ˇcells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.