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,
*
Department of Immunology, St. James’s Hospital, Dublin, Ireland;
Education and Research Center and
Liver Unit, St. Vincent’s University Hospital and Conway Institute, University College Dublin, Dublin, Ireland; and
Institute of Immunology, Department of Biology, National University of Ireland, Maynooth, Ireland
IL-2 and IL-15 are lymphocyte growth factors produced by different
cell types with overlapping functions in immune responses. Both
cytokines costimulate lymphocyte proliferation and activation, while
IL-15 additionally promotes the development and survival of NK cells,
NKT cells, and intraepithelial lymphocytes. We have investigated the
effects of IL-2 and IL-15 on proliferation, cytotoxicity, and cytokine
secretion by human PBMC subpopulations in vitro. Both cytokines
selectively induced the proliferation of NK cells and CD56+
T cells, but not CD56- lymphocytes. All NK and
CD56+ T cell subpopulations tested (CD4+,
CD8+, CD4-CD8-,
TCR+, 
TCR+, CD16+,
CD161+, CD158a+, CD158b+,
KIR3DL1+, and CD94+) expanded in response to
both cytokines, whereas all CD56- cell subpopulations did
not. Therefore, previously reported IL-15-induced and
CD8+ T cell expansions reflect proliferations of NK and
CD56+ T cells that most frequently express these
phenotypes. IL-15 also expanded CD8+-
and V24V11 TCR+ T cells. Both cytokines stimulated
cytotoxicity by NK and CD56+ T cells against K562 targets,
but not the production of IFN-, TNF-, IL-2, or IL-4. However,
they augmented cytokine production in response to phorbol ester
stimulation or CD3 cross-linking by inducing the proliferation of NK
cells and CD56+ T cells that produce these cytokines at
greater frequencies than other T cells. These results indicate that
IL-2 and IL-15 act at different stages of the immune response by
expanding and partially activating NK receptor-positive lymphocytes,
but, on their own, do not influence the Th1/Th2 balance of adaptive
immune responses.
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