IL-15 is a growth factor and an activator of CD8 memory T cells

Memory lymphocytes, arising from naive lymphocytes after antigenic stimulation and being long-lived, are the cellular basis for immunological memory. Recent studies of CD8 T cells suggest that generation of CD8 memory T cells requires the engagement of T cell antigen receptors (TCR) with antigen, yet the maintenance of CD8 memory T cells appears to be dependent on cytokines, such as IL-15, independent of TCR. Although considerable progress has been made in understanding the molecular and cellular events of TCR-induced differentiation and proliferation in the past decade, less is known about the mechanisms of IL-15 action. From a kinetic and comparative analysis of the responses of memory phenotype CD8 T cells to IL-15 and TCR stimulation in vitro, we found that IL-15 and anti-CD3 induce highly similar responses in memory phenotype CD8 T cells as measured by general gene expression profiles, synthesis of effector molecules (IFNgamma, TNFbeta, granzyme B and perforin), induction of cytotoxicity, and cellular proliferation. These findings indicate that IL-15 is not only a growth factor but also an antigen-independent activator for CD8 memory T cells.