Elsevier

Human Immunology

Volume 28, Issue 2, June 1990, Pages 112-118
Human Immunology

High proliferative capacity and specific antiautologous melanoma cytotoxicity of a human t-lymphocyte clone derived from tumor-infiltrating lymphocytes

https://doi.org/10.1016/0198-8859(90)90006-BGet rights and content

Abstract

A CD8+ clone, identified by its T-cell receptor γ- and β-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 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 C on A blast or allogeneic tumor targets. Furthermore, specific killing was inhibited by monoclonal antibodies against CD3, CD8, T-cell receptors αβ, 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 obtainedfrom melanoma TIL and that a single cytotoxic T lymphocyte clone can be expanded to more than 1010 cells without a loss of autotumor specificity.

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