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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-01-0183.
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Blood, 1 October 2003, Vol. 102, No. 7, pp. 2541-2546
IMMUNOBIOLOGY
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
René A. W. van Lier
From the Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Molecular Immunology, Institute for Molecular and Cell Biology, Porto, Portugal; and Sanquin Research, Amsterdam, the Netherlands.
Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8+ T cells, it has no apparent function in controlling homeostatic proliferation 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 interferon  (IFN-) and tumor necrosis factor  (TNF-), expressed perforin and granzyme B, and acquired cytotoxic properties. Primed CD8+ T cells, from both noncytotoxic (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. (Blood. 2003;102:2541-2546)
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