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Development of autologous cytotoxic CD4 + T clones in a human model of B‐cell non‐Hodgkin follicular lymphoma
Author(s) -
Mi JianQing,
Manches Olivier,
Wang Jin,
Perron Pascal,
Weisbuch Sébastien,
Marche Patrice N.,
Renversez JeanCharles,
Bensa JeanClaude,
Sotto JeanJacques,
Cahn JeanYves,
Leroux Dominique,
Bonnefoix Thierry
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06294.x
Subject(s) - cytotoxic t cell , follicular lymphoma , immunology , biology , cd8 , immunodominance , antigen , adoptive cell transfer , interleukin 21 , lymphoma , t cell , cancer research , epitope , immune system , in vitro , biochemistry
Summary 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 V β 17‐D β 1‐J β 1·2 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.