title: Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity.
abstract: Improving the potency of immune responses is paramount among issues concerning vaccines against deadly pathogens. IL-28B belongs to the newly described interferon lambda (IFNlambda) 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.forename: Panyupa
authors.initials: P
authors.lastname: Pankhong
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Laddy
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Schoenly
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Neil
authors.initials: N
authors.lastname: Cisper
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000220:Adaptation, Biological / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015683:Gene Products, gag / Q000494:pharmacology; D007111:Immunity, Cellular / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014611:Vaccination; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D015683:Gene Products, gag; D007074:Immunoglobulin G; D007371:Interferon-gamma; D018664:Interleukin-12; D016212:Transforming Growth Factor beta; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda