title: Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells.
abstract: In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.
authors.affiliation: Oncogénèse Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Sahraoui
authors.forename: M
authors.initials: M
authors.lastname: Allouche
authors.forename: A
authors.initials: A
authors.lastname: Ammar
authors.forename: E
authors.initials: E
authors.lastname: Spanakis
authors.forename: C
authors.initials: C
authors.lastname: Clemenceau
authors.forename: C
authors.initials: C
authors.lastname: Jasmin
authors.forename: M
authors.initials: M
authors.lastname: Perraki
authors.forename: C
authors.initials: C
authors.lastname: Varela-Millot
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2