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.
Lu
Jun
J
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Giuntoli
Robert L
RL
Omiya
Ryusuke
R
Kobayashi
Hiroya
H
Kennedy
Richard
R
Celis
Esteban
E
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit; D008213:Lymphocyte Activation / Q000187:drug effects*; D009369:Neoplasms / Q000276:immunology*; D018123:Receptors, Interleukin / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015789:HLA-A2 Antigen; C508017:IL2RA protein, human; C508018:Il2ra protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin