IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretion

• Published in: Immunobiology (1979) Vol. 216; no. 5; pp. 604 - 612
• Main Authors: Correia, Margareta P, Costa, Alexandra V, Uhrberg, Markus, Cardoso, Elsa M, Arosa, Fernando A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.05.2011
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; Antibodies, Monoclonal - pharmacology; CD56 Antigen - biosynthesis; CD56 Antigen - genetics; CD56 Antigen - immunology; CD8+ T cells; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cytokines; Cytotoxicity, Immunologic; Differentiation; Granzymes - genetics; Granzymes - metabolism; Humans; IL-15; Immunologic Memory; Interleukin-15 - immunology; Interleukin-15 - metabolism; K562 Cells; Mice; Natural Killer T-Cells - cytology; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; NK Cell Lectin-Like Receptor Subfamily C - immunology; NK Cell Lectin-Like Receptor Subfamily K - immunology; NK receptors; Perforin - genetics; Perforin - metabolism; Receptors, KIR - immunology; CD8+ T cells; Cytokines; natural cytotoxicity receptor; IL-15; NKG2; NK receptor; NKR; KIR; killer immunoglobulin-like receptor; NK receptors; NCR; Differentiation; natural killer cell lectin-like receptor gene 2
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2010.09.012

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.