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The Journal of Immunology, 1998, 161: 5578-5585.
Copyright © 1998 by The American Association of Immunologists

Evaluation of IL-12 in Immunotherapy and Vaccine Design in Experimental Mycobacterium avium Infections1

Regina A. Silva, Teresa F. Pais and Rui Appelberg2

Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal

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.




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