title: Suppression of high affinity IL-2 receptors on mitogen activated lymphocytes by glioma-derived suppressor factor.
abstract: Previously we have reported that human glial tumor cells secrete a factor(s) which suppresses the mitogen responsiveness of normal human peripheral blood lymphocytes (PBL) in a dose dependent manner. In this study we extend these observations and explore the possible mechanisms by which glioma-derived suppressor factor(s) (GSF) modulates lymphocyte reactivity. Preincubation of lymphocytes with GSF for 2 hrs induces suppression of lymphocyte mitogen responsiveness. GSF also inhibits production of interleukin-2 (IL-2) by mitogen activated human T-cells. Addition of delectinated or recombinant IL-2 to mitogen activated human T-cells in the presence of GSF does not restore the normal proliferative response of these cells. These findings suggest that GSF induces a defect in the expression of the receptor for IL-2 (IL-2R) on activated T-cells. Binding studies with radiolabeled IL-2 demonstrated that GSF suppresses and in some cases completely inhibits the expression of functional high affinity IL-2R on activated T-cells, thereby, preventing association of IL-2R with its receptor and the subsequent progression of the cell into the proliferative stage of the cell cycle. These cellular defects induced by GSF closely parallel the observed defects noted in T-cells obtained from patients with gliomas, indicating that the factors elicited from glial tumors may be responsible for the immunological deficits observed in patients with primary malignant intracranial tumors.
authors.affiliation: Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084.
authors.forename: L H
authors.initials: LH
authors.lastname: Elliott
authors.forename: W H
authors.initials: WH
authors.lastname: Brooks
authors.forename: T L
authors.initials: TL
authors.lastname: Roszman
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015213:Neuroimmunomodulation; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D001685:Biological Factors; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2