Regulation of human cytolytic lymphocyte responses by interleukin-12

Cell Immunol. 1992 Aug;143(1):127-42. doi: 10.1016/0008-8749(92)90011-d.


IL-12 is a heterodimeric cytokine which has been shown to cause the proliferation of activated T and NK cells, to enhance the lytic activity of NK cells, and to induce IFN-gamma production by resting and activated T and NK cells. We previously reported that IL-12 could synergize with IL-2 to activate human LAK cells in the presence of hydrocortisone but that IL-12 alone was inactive. We herein show that in the absence of hydrocortisone, IL-12 by itself can activate human LAK cells. IL-12-induced LAK cell activity was mediated predominantly by CD56+ lymphocytes. Activation of LAK cells by IL-12 appeared to be independent of IL-2 since it was not inhibited by neutralizing anti-human IL-2. However, IL-12- and IL-2-induced LAK cell activation could be partially inhibited by anti-human TNF-alpha. Moreover, IL-12 produced in situ appeared to play a role in IL-2-induced LAK cell activation since rat monoclonal antibodies to human IL-12 could partially inhibit the generation of LAK cells in response to IL-2. In addition to its effects on LAK cell responses, IL-12 could facilitate specific allogeneic human CTL responses. However, IL-12-facilitated CTL responses were blocked by neutralizing anti-human IL-2 indicating a requirement for IL-2 produced in situ. The ability of IL-12 to facilitate both nonspecific LAK and specific CTL responses suggests that it may be useful as a therapeutic agent against some tumors and infectious diseases.

MeSH terms

  • Cells, Cultured
  • Humans
  • Interferon-gamma / physiology
  • Interleukin-12
  • Interleukin-2 / physiology
  • Interleukins / pharmacology*
  • Killer Cells, Lymphokine-Activated / drug effects*
  • Killer Cells, Lymphokine-Activated / physiology
  • Lymphocyte Activation / drug effects
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / physiology
  • Tumor Necrosis Factor-alpha / physiology


  • Interleukin-2
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma