Interleukin-12: a pivotal regulator of cell-mediated immunity.

Abstract

Interleukin-12 (IL-12) is heterodimeric cytokine which is produced by antigen-presenting cells and serves as a pivotal regulator of T- and NK-cell function. IL-12 was identified independently by investigators at the Wistar Institute [1] and at Hoffmann-La Roche [2], who originally called it natural killer cell stimulatory factor (NKSF) [1] or cytotoxic lymphocyte maturation factor (CLMF) [2], respectively. Cloning of the cDNAs encoding the proteins mediating these 2 activities showed that NKSF and CLMF were the same molecule [3,4], which is now generally referred to as IL-12. The biologic activities initially associated with IL-12 include its ability to enhance the lytic activity of natural killer/lymphokine-activated killer (NK/LAK) cells [1,2], to induce the secretion of interferon-γ (IFN-γ) by both resting and activated T and NK cells [1,5], to stimulate the proliferation of activated T and NK cells [2,6], and to facilitate cytolytic T-lymphocyte (CTL) responses [7,8]. All of these activities are shared by IL-12 with other interleukins such as IL-2. However, IL-12 has more recently been found to play a critical and unique role in promoting TH1-type cytokine responses [9,10], thereby facilitating cell-mediated immunity. The immunoenhancing effects of IL-12 on T and NK cell function provide the basis for its therapeutic effects in a number of mouse tumor models and models of infectious diseases.KeywordsNatural Killer ActivitySoluble Leishmania AntigenRenca TumorStaphylococcus Aureus CowanNatural Killer Cell Stimulatory FactorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.