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 Blood, 4 June 2009, Vol. 113, No. 23, pp. 5868-5877.
Prepublished online as a Blood First Edition Paper on March 20, 2009; DOI 10.1182/blood-2008-11-190520.

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IMMUNOBIOLOGY

Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity

Matthew P. Morrow1, Panyupa Pankhong1, Dominick J. Laddy1, Kimberly A. Schoenly1, Jian Yan1, Neil Cisper1, and David B. Weiner1

1 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia

Improving the potency of immune responses is paramount among issues concerning vaccines against deadly pathogens. IL-28B belongs to the newly described interferon lambda (IFN{lambda}) family of cytokines, and has not yet been assessed for its potential ability to influence adaptive immune responses or act as a vaccine adjuvant. We compared the ability of plasmid-encoded IL-28B to boost immune responses to a multiclade consensus HIV Gag plasmid during DNA vaccination with that of IL-12. We show here that IL-28B, like IL-12, is capable of robustly enhancing adaptive immunity. Moreover, we describe for the first time how IL-28B reduces regulatory T-cell populations during DNA vaccination, whereas IL-12 increases this cellular subset. We also show that IL-28B, unlike IL-12, is able to increase the percentage of splenic CD8+ T cells in vaccinated animals, and that these cells are more granular and have higher antigen-specific cytolytic degranulation compared with cells taken from animals that received IL-12 as an adjuvant. Lastly, we report that IL-28B can induce 100% protection from mortality after a lethal influenza challenge. These data suggest that IL-28B is a strong candidate for further studies of vaccine or immunotherapy protocols.


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