IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretion
- a IBMC – Instituto de Biologia Molecular e Celular, Porto, Portugal
- b ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal
- c Centro de Investigação em Ciências da Saúde (CICS), Instituto Superior de Ciências da Saúde Norte, CESPU, Portugal
- d University Clinic of Düsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics, Düsseldorf, Germany
- Received 19 August 2010, Revised 15 September 2010, Accepted 20 September 2010, Available online 24 September 2010
Abstract
During the last years several authors have described a small population of CD8+ T cells expressing NK receptors (NKRs). Although their origin remains largely unknown, we have recently demonstrated that IL-15 is capable of inducing NKR expression in purified human CD8+CD56− T cells. In this study we show that IL-15-driven NKR induction in CD8+ T cells was linked with CD56 de novo acquisition, consistent with an effector-memory phenotype, increased anti-apoptotic levels, high granzyme B/perforin expression and with the ability of displaying in vitro NK-like cytotoxicity. Interestingly, dissection of NKR functional outcome in IL-15-cultured CD8+ T cells revealed: (i) that NKG2D cross-linking was able per se to upregulate degranulation levels and (ii) that KIR and NKG2A cross-linking upregulated secretion of cytokines such as IFN-γ, TNF-α, IL-1β and IL-10. These results suggest that IL-15 is capable of differentiating CD8+ T cells into NK-like T cells displaying a regulatory phenotype.
Abbreviations
- KIR, killer immunoglobulin-like receptor;
- NCR, natural cytotoxicity receptor;
- NKG2, natural killer cell lectin-like receptor gene 2;
- NKR, NK receptor
Keywords
- CD8+ T cells;
- Cytokines;
- Differentiation;
- IL-15;
- NK receptors
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