Human Interleukin-12 Enhances Interferon-γ—Producing Influenza-Specific Memory CD8+ Cytotoxic T Lymphocytes

• Published in: The Journal of infectious diseases 1999-11, Vol.180 (5), p.1477-1486
• Main Authors: Mbawuike, Innocent N., Fujihashi, Kohtaro, DiFabio, Simonetta, Kawabata, Shigetada, McGhee, Jerry R., Couch, Robert B., Kiyono, Hiroshi
• Format: Article
• Language: English
• Subjects: Adult; Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell interactions; Child; Cytokines; Cytotoxicity, Immunologic; Enzyme-Linked Immunosorbent Assay - methods; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunologic Memory; Influenza A virus - immunology; Interferon-gamma - biosynthesis; Interferons; Interleukin-12 - immunology; Interleukins; Leukocyte Common Antigens - analysis; Lymphocyte Activation; Lymphocytes; Major Articles; Male; Memory; Messenger RNA; Microbiology; Orthomyxoviridae; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - metabolism; T lymphocytes; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - immunology; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315090

Interferon (IFN)—γ synthesis of CD45RO+ (memory) and CD45RA+ (naive) CD8+ cytotoxic T lymphocytes (CTLs) and the role of interleukin (IL)—12 in the regulation of human CTL functions in virus-specific immunity were investigated. After culture with influenza virus, CD45RO+ CD8+ T cells from human peripheral blood mononuclear cells increased in frequency and exhibited significant major histocompatibility complex class I—mediated CTL activity, whereas CD45RA+ CD8+ T cells did not. Influenza virus—stimulated CD45RO+ CD8+ T cells contained significantly higher levels of IFN-γ—producing cells and IFN-γ—specific mRNA than did CD45RA+ CD8+ T cells. Recombinant human IL-12 further enhanced CTL activity and IFN-γ production by CD45RO+ CD8+ T cells. These data clearly show that human virus-specific CTL activity and coproduction of IFN-γ are associated with the CD45RO+ CD8+ T cells that are modulated by the cell-mediated, immunity-inducible cytokine IL-12 in humans.