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Human antitumor CD8+ T cells producing Th1 polycytokines show superior antigen sensitivity and tumor recognition

Item Type:Article
Title:Human antitumor CD8+ T cells producing Th1 polycytokines show superior antigen sensitivity and tumor recognition
Creators Name:Wilde, S. and Sommermeyer, D. and Leisegang, M. and Frankenberger, B. and Mosetter, B. and Uckert, W. and Schendel, D.J.
Abstract:Adoptive transfer of T cells expressing transgenic TCR with antitumor specificity provides a hopeful new therapy for patients with advanced cancer. To fulfill a large need for TCR with high affinity and specificity for various tumor entities, we sought to identify parameters for rapid selection of CTL clones with suitable characteristics. Twelve CTL clones displaying different Ag sensitivities for the same peptide-MHC epitope of the melanoma-associated Ag tyrosinase were analyzed in detail. Better MHC-multimer binding and slower multimer release are thought to reflect stronger TCR-peptide-MHC interactions; thus, these parameters would seem well suited to identify higher avidity CTL. However, large disparities were found comparing CTL multimer binding with peptide sensitivity. In contrast, CD8(+) CTL with superior Ag sensitivity mediated good tumor cytotoxicity and also secreted the triple combination of IFN-gamma, IL-2, and TNF-alpha, representing a Th1 pattern often missing in lower avidity CTL. Furthermore, recipient lymphocytes were imbued with high Ag sensitivity, superior tumor recognition, as well as capacity for Th1 polycytokine secretion after transduction with the TCR of a high-avidity CTL. Thus, Th1 polycytokine secretion served as a suitable parameter to rapidly demark cytotoxic CD8(+) T cell clones for further TCR evaluation.
Keywords:Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Adhesion, Cell Line, Clone Cells, Coculture Techniques, Cultured Cells, Cytokines, Immunologic Cytotoxicity, Neoplasm Antigens, Th1 Cells, Tumor Cell Line
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:598-605
Date:15 July 2012
Additional Information:Authors' reply in J Immunol 189(8): 3787.
Official Publication:https://doi.org/10.4049/jimmunol.1102165
PubMed:View item in PubMed

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