High proliferative capacity and specific antiautologous melanoma cytotoxicity of a human T-lymphocyte clone derived from tumor-infiltrating lymphocytes.
A CD8+ clone, identified by its T-cell receptor gamma- and beta-gene configuration, was shown to preferentially develop, in the bulk culture of melanoma tumor-infiltrating lymphocytes with recombinant interleukin 2 after 1 month. Thirteen CD8+ clones were obtained by limiting dilution culture of tumor-infiltrating lymphocytes from 43-days old culture. Four of these clones, analyzed for T-cell receptor rearrangements, exhibited exactly the same T-cell receptor gene pattern as tumor-infiltrating lymphocytes from the bulk culture, showing, therefore, that all the CD8+ clones were subclones. All the 13 CD8+ subclones were strongly cytotoxic for autologous melanoma cells but did not kill K562. A more complete cytotoxicity analysis showed that the clones did not kill autologous fibroblasts or Con A blasts or allogeneic tumor targets. Furthermore, specific killing was inhibited by monoclonal antibodies against CD3, CD8, T-cell receptors alpha beta, and class I major histocompatibility complex antigens indicating that effector-to-target cell recognition was mediated through the T-cell receptor in a major histocompatibility complex-restricted fashion. These data showed that human melanoma-specific cytotoxic T lymphocytes can be obtained from melanoma TIL and that a single cytotoxic T lymphocyte clone can be expanded to more than 10(10) cells without a loss of autotumor specificity.
Gervois
N
N
Unité 211 INSERM, Laboratoire d'Immunologie, Faculté des Sciences de Nantes, France.
Heuze
F
F
Diez
E
E
Jotereau
F
F
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D016827:CD8 Antigens; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell