Interleukin 15 promotes antigen-independent in vitro expansion and long-term survival of antitumor cytotoxic T lymphocytes.

The survival and expansion of effector cytotoxic T lymphocytes (CTLs) during an immunological response are critical for the successful elimination of life-threatening attacks by microorganisms, parasites, or malignant cells. Among the numerous factors that regulate the immune response, interleukin (IL)-2, and its close relative, IL-15 are known to function as growth and survival factors for antigen-experienced T cells. However, major differences appear to exist between these lymphokines in their capacity to act on various T-cell types such as CD4+ versus CD8+ or effector versus memory T lymphocytes. Although several studies have been done in the mouse system, less information is available regarding the function of these lymphokines in the human system. Here, we report that IL-15 or high concentrations of IL-2 induced antigen-independent expansion of effector CD8+ CTLs. Neither IL-2 nor IL-15 induced the proliferation of CD4+ T cells. In the absence of antigen, at least one of these lymphokines was required for the long-term survival of the cells in tissue culture. Most significantly, the effector cytolytic activity of CTLs expanded and maintained in IL-15 for up to 60 days remained stable, indicating that these cells do not differentiate into a memory functional phenotype. The expression of IL-15Ralpha, which was detected on CD8+ CTLs but not on CD4+ helper T cells, suggests that this receptor subunit somehow participates in the transduction of the mitogenic signals of IL-15. The present findings have practical implications for the propagation of antigen-specific T-cell lines in vitro and could be useful for expansion of therapeutic T cells for adoptive transfer.