IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretion.
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.
IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.
Margareta P
MP
Correia
Alexandra V
AV
Costa
Markus
M
Uhrberg
Elsa M
EM
Cardoso
Fernando A
FA
Arosa
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019002:CD56 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D020014:K562 Cells; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology
D000911:Antibodies, Monoclonal; D019002:CD56 Antigen; D019409:Interleukin-15; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D054340:Receptors, KIR; D054353:Perforin; D053804:Granzymes