IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro.
CD8+ cytolytic T lymphocytes (CTLs) are important mediators for resistance to infections and malignant diseases. IL-12 enhances proliferative and cytolytic responses by killer cells, but its function in the generation of human antiviral CD8+ T cell responses has not been defined. We therefore evaluated the role of IL-12 in the generation of CTLs to influenza-infected dendritic cells. IL-12 was not detectable in supernatants of infected-dendritic cells, or during CTL generation. Furthermore, anti-IL-12 antibody did not block CTL generation. However, exogenous IL-12 (30-300 pg/ml) enhanced CD8+ T cell proliferative and cytolytic responses. The effect was greatest in individuals with weak reactivity to influenza virus or at antigen-presenting cell (APC):T cell ratios of 1:100 or less. IL-12 augmented interferon-gamma production during CTL generation. The CTL enhancing effects of the cytokine, however, could not be blocked by neutralizing anti-interferon-gamma antibody. Together with IL-12, antigen-pulsed dendritic cells may be a useful approach for boosting CTL responses against infectious agents and malignancies.
Bhardwaj
N
N
Rockefeller University, New York 10021, USA.
Seder
R A
RA
Reddy
A
A
Feldman
M V
MV
D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009975:Orthomyxoviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma