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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-01-0183.
Submitted January 22, 2003
Accepted May 29, 2003
IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro
Nuno L Alves*, Berend Hooibrink, Fernando A Arosa, and Rene A van Lier
Laboratory for Experimental Immunology, Academical Medical Center, Amsterdam, The Netherlands; Laboratory of Molecular Immunology, Institute for Molecular and Cell Biology, Porto, Portugal
Sanquin Research, Amsterdam, The Netherlands
Laboratory of Molecular Immunology, Institute for Molecular and Cell Biology, Porto, Portugal
Laboratory for Experimental Immunology, Academical Medical Center, Amsterdam, The Netherlands
* Corresponding author; email: n.m.lagesalves{at}amc.uva.nl.
Recent studies in mice have shown that although IL-15 plays an important role in regulating homeostasis of memory CD8+ T cells it has no apparent function in controlling homeostatic proliferation and survival of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15. In this process, naive CD8+ T cells successively down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with these phenotypic changes, naive cells acquired the ability to produce IFN- and TNF- , expressed perforin and granzyme B and acquired cytotoxic properties. Primed CD8+ T cells, from both non-cytotoxic (CD45RA-CD27+) and cytotoxic (CD45RA+CD27-) subsets, responded to IL-15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells. In summary, all human CD8+ T-cell subsets had the ability to respond to IL-15, which suggests a generic influence of this cytokine on CD8+ T-cell homeostasis in man.
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