Abstract
Interleukin-12 (IL-12) is a B-cell and monocyte-derived 75 kDa het-erodimeric cytokine released early after immune stimulation. It promotes the cytolytic maturation and proliferation of T and natural killer (NK) cells and release of interferon-γ from these effectors. Furthermore, IL-12 appears to stimulate the production of a Thl immune response. We have examined the effects of IL-12 on the proliferation and lytic activity of fresh peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs). IL-12 stimulates proliferation of PBMCs by as much as 10–fold after T-cell receptor (TCR) ligation induced by anti-CD3 or phytohemagglutinin. In contrast, IL-12 promotes only marginal proliferation of resting PBMCs. IL-12 modulates IL-2-induced lymphokine-activated killer (LAK) cell activity: It inhibits IL-2 LAK when added early to culture but augments LAK activity in PBMCs preactivated by IL-12. IL-12 induces the proliferation (three- to fourfold above background) and enhances the cytolytic activity (two- to fourfold) of TIL lines and melanoma-derived, peptide-specific T-cell clones that have been recently restimulated with autologous tumor. These results suggest that IL-12 may serve in vivo to amplify and focus the cellular immune response by selectively inducing the outgrowth and enhancing the lytic potential of T and NK cells that have received the proper coactivation signals.
Original language | English (US) |
---|---|
Pages (from-to) | 155-161 |
Number of pages | 7 |
Journal | Journal of Immunotherapy |
Volume | 14 |
Issue number | 2 |
DOIs | |
State | Published - Aug 1993 |
Externally published | Yes |
Keywords
- Immune effectors
- Interleukin-12
- Lymphokine-activated killer cells
- Natural killer cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
- Cancer Research