Generation of Melan-A/MART-1-specific CD8+ cytotoxic T lymphocytes from human naive precursors: Helper effect requirement for efficient primary cytotoxic T lymphocyte induction in vitro
✍ Scribed by Marina Ostankovitch; Frédérique-Anne Le Gal; Francine Connan; Dorine Chassin; Jeannine Choppin; Jean-Gérard Guillet
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 162 KB
- Volume
- 72
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
This study investigates the generation of primary melanoma cell-specific cytotoxic T lymphocytes (CTLs) in vitro. Induction of peptide-specific CTLs from unfractionated naive peripheral blood mononuclear cells from HLA-A2 healthy donors was assessed using 2 recently described 9-mer epitopes from the melanoma tumor antigen Melan-A/MART-1. The need for help from CD4 ؉ T lymphocytes for the longlasting induction of CTLs and the capacity of the peptideinduced CTL lines to recognize many melanoma cells were evaluated. CTL lines were obtained reproducibly when CD4 ؉ T-lymphocyte help was provided during the primary stimulation either in an autologous way, in the case of tetanus toxoid antigen (TT) responder donors, or with allogeneic TTactivated T-helper cells, separated by an insert well, in the case of tetanus toxoid non-responder donors. We also investigated helper T-cell-derived factors that are produced by TT-activated lymphocytes. Our results strongly suggest that a complex network of cytokines like interleukin-2 (IL-2), interferon-␥, IL-6 and IL-1 exerts stimulatory effects for the initiation process of CTLs. In contrast, cytokine-like IL-4 might inhibit generation of cytolytic activity if provided by TT-activated T cells at early stages of induction. Our approach can be used to generate CTLs of a desired specificity for clinical use in adoptive immunotherapy protocols.