title: Restoration of cytotoxic T lymphocyte function in malignant pleural effusion: interleukin-15 vs. interleukin-2.
abstract: The present study attempts to define the role of interleukin-15 (IL-15), as compared with IL-2, in generating cytotoxic T lymphocytes (CTL) from the malignant effusions of cancer patients. Effusion-associated lymphocytes (EAL) from malignant effusion were incubated with IL-15 or IL-2 with or without alphaCD3. Proliferation and cytotoxicity assays were performed. IL-15 was found to have at least an equivalent, if not higher, activity to IL-2 in terms of lymphocyte proliferation and generation of CTL from EAL. The proliferative response of EAL, cocultured with IL-15, with or without alphaCD3, was partly inhibited by pretreatment with an anti-IL2 receptor beta chain monoclonal antibody (mAb). The proliferative response of EAL, cocultured with alphaCD3, IL-2, or both, was partly inhibited by pretreatment with an anti-IL-2 receptor alpha chain mAb. Overnight [5lCr] release assays against K562, Daudi, and the patients' autologous tumor cells were done to evaluate EAL's cytolytic activity. MHC class I Ab blocked the stimulated cytolytic activity of EAL against autologous tumors. An mAb depletion assay showed that the phenotype of the restored EAL was CD16-CD4-CD8+; thus, the restored activity of EAL was CTL activity. The results suggest that both IL-15 and IL-2 can restore CTL activity from EAL in the presence of T cell receptor (TCR)-CD3 engagement, but the effect of IL-15 was superior.
authors.affiliation: Chest Department, Veterans' General Hospital-Taipei, School of Medicine, National Yang-Ming University, Taiwan. ymchen@vghtpe.gov.tw
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: C C
authors.initials: CC
authors.lastname: Ting
authors.forename: J W
authors.initials: JW
authors.lastname: Peng
authors.forename: W K
authors.initials: WK
authors.lastname: Yang
authors.forename: K Y
authors.initials: KY
authors.lastname: Yang
authors.forename: C M
authors.initials: CM
authors.lastname: Tsai
authors.forename: R P
authors.initials: RP
authors.lastname: Perng
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D016853:Muromonab-CD3 / Q000494:pharmacology; D016066:Pleural Effusion, Malignant / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D007376:Interleukin-2; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins