title: Development of autologous cytotoxic CD4+ T clones in a human model of B-cell non-Hodgkin follicular lymphoma.
abstract: Immunotherapy for cancer aims to generate cytotoxic cells that are capable of eradicating tumour cells. It has been well demonstrated that helper, non-cytotoxic CD4(+) T cells are important for the induction and maintenance of anti-tumour immunity exerted by cytotoxic CD8(+) T cells. In contrast, the existence of direct anti-tumour, effector cytotoxic CD4(+) T cells remains elusive, mainly due to the paucity of reliable experimental data, especially in human B-cell non-Hodgkin lymphomas. This study developed an appropriate, autologous follicular B-cell non-Hodgkin follicular lymphoma model, including the in vitro establishment of a malignant, human leucocyte antigen class I (HLA-I) deficient B-cell line, and the generation of three autologous anti-tumour cytotoxic CD4(+) T-cell clones originating from the peripheral blood of the same patient. These three clones were considered as tumour specific, because they were capable of killing the malignant, HLA-I-deficient B-cell line through a classical HLA-II restricted perforin-mediated pathway, but did not lyse the Epstein-Barr virus-infected autologous normal B lymphocytes. All three CD4(+)clones were T-cell receptor Vbeta17-Dbeta1-Jbeta1.2 and exhibited an identical complementarity-determining region 3, suggesting the immunodominance of a single peptide antigen presented by tumour cells. Such lymphoma models would provide a useful tool for in vivo expansion and the adoptive transfer of selected CD4(+) cytotoxic cells in immunotherapeutic strategies.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)], Université Joseph Fourier, La Tronche, France. jian-qing.mi@ujf-grenoble.fr
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Mi
authors.forename: Olivier
authors.initials: O
authors.lastname: Manches
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Pascal
authors.initials: P
authors.lastname: Perron
authors.forename: Sébastien
authors.initials: S
authors.lastname: Weisbuch
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Renversez
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bensa
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Sotto
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.forename: Thierry
authors.initials: T
authors.lastname: Bonnefoix
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000276:immunology*; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell