Enhancement of natural killer cell activation and antibody-dependent cellular cytotoxicity by interferon-alpha and interleukin-12 in vaginal mucosae Sivmac251-infected Macaca fascicularis.
We studied the innate immune system of Cynomolgus monkeys (Macaca fascicularis) experimentally infected via the vaginal mucosae with a virulent simian immunodeficiency virus isolate SIVmac251. Animals were evaluated for their natural killer (NK) cell activity, and for their antibody-dependent cellular cytotoxicity. NK cells from SIVmac251-infected macaques show impaired NK cell activity compared to cells from uninfected animals. Subsequent treatment of NK cells with interferon-a (IFN-alpha) or interleukin-12 (IL-12) alone partially restored the NK activity. However, either treatment of NK cells with both IFN-alpha and IL-12 completely reversed the impairment of cytotoxicity induced by simian immunodeficiency virus (SIV) infection. Incubation of NK cells from infected but not from uninfected monkeys with IFN-alpha and IL-12 for 8 days increased the percentage of CD16+/CD56+ cells twofold to five-fold and enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. Thus IFN-alpha and IL-12 greatly enhance both the NK cell and ADCC activities of peripheral blood cells from SIVmac251-infected animals and increase the number of NK cells in longer term culture. The combined effect of IFN-alpha and IL-12 in enhancing NK cell activity may provide a novel therapeutic approach for the restoration of depressed NK cell activity observed in human immunodeficiency virus (HIV)-infected patients.
Poaty-Mavoungou
Virginie
V
Centre International de Recherches Médicales de Franceville, Gabon.
Touré
Fousseyni S
FS
Tevi-Benissan
Carol
C
Mavoungou
Elie
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D019002:CD56 Antigen / Q000032:analysis; D005260:Female; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D018664:Interleukin-12 / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008252:Macaca fascicularis; D009092:Mucous Membrane / Q000821:virology; D017452:Receptors, IgG / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D014621:Vagina / Q000821:virology*
D000276:Adjuvants, Immunologic; D019002:CD56 Antigen; D019302:HIV Envelope Protein gp160; D016898:Interferon-alpha; D017452:Receptors, IgG; D018664:Interleukin-12