Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells

Citation
Yw. Li et al., Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells, BLOOD, 96(8), 2000, pp. 2828-2833
Citations number
18
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
0006-4971 → ACNP
Volume
96
Issue
8
Year of publication
2000
Pages
2828 - 2833
Database
ISI
SICI code
0006-4971(20001015)96:8<2828:TROHMC>2.0.ZU;2-A
Abstract
Immunoglobulin secreted by myeloma cells contains a unique antigenic determ inant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with my eloma, it is not known whether primary myeloma tumor cells can present natu rally processed Id peptides on their surface as a target. We immunized 2 he althy human stem-cell donors with Id proteins from their recipients. T cell s from the immunized donors released high levels of T-helper I-type cytokin es in response to stimulation with myeloma cells from their recipients, The T-cell-mediated cytokine response to tumor cells was blocked by a major hi stocompatibility complex (MHC) class I monoclonal antibody, whereas the res ponse to soluble Id protein was dependent on MHC class II. To investigate w hether id-specific CD8(+) T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologou s dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma c ells was demonstrated by the lack of killing of autologous nonmalignant B c ells or natural killer-sensitive K562 cells. Lysis of autologous myeloma ta rgets was restricted by MHC class I molecules. These data represent the fir st report of class I-restricted T-cell recognition of fresh autologous myel oma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response. (C) 2000 by The American Society of Hematology.