Evaluation of IL-12 in immunotherapy and vaccine design in experimental Mycobacterium avium infections.
IL-12 is a pivotal cytokine in the induction of IFN-gamma-mediated protective immune responses. We tested the effects of rIL-12 administration to Mycobacterium avium-infected mice and found a limited ability to induce protection against the infection; this ability varied according to the mycobacterial strain studied. IL-12 accelerated the expression and production of IFN-gamma in both immunocompetent and immunodeficient SCID or CD4-depleted mice. Evidence of NK cell activation was found as well as an enhancement of the ability to adoptively transfer resistance with T cell-enriched spleen cell populations and an increase in inflammatory cell recruitment in the liver. The protective ability of IL-12 was dependent upon the endogenous production of IFN-gamma as evaluated by the use of specific neutralizing Abs or IFN-gamma gene-disrupted mice. IL-12 potentiated the protective immunity conferred by a subunit vaccine containing M. avium culture filtrate proteins and dimethyl dioctadecyl ammonium chloride as an adjuvant. Thus, we show limited immunotherapeutic benefits from IL-12 administration in M. avium infections and promising results in its use as a coadjuvant in vaccine design.
Silva
R A
RA
Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Portugal.
Pais
T F
TF
Appelberg
R
R
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000235:genetics / Q000627:therapeutic use; D000818:Animals; D001428:Bacterial Vaccines / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D015195:Drug Design; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009162:Mycobacterium avium / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D018664:Interleukin-12