title: IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques.
abstract: Type III/lambda interferons (IFNs) were discovered less than a decade ago and are still in the process of being characterized. Although previous studies have focused on the function of IFN-lambda 3 (also known as interleukin (IL)-28B) in a small animal model, it is unknown whether these functions would translate to a larger, more relevant model. Thus in the present study, we have used DNA vaccination as a method of studying the influence of IFN-lambda 3 on adaptive immune responses in rhesus macaques. Results of our study show for the first time that IFN-lambda 3 has significant influence on antigen-specific CD8(+) T-cell function, especially in regards to cytotoxicity. Peripheral CD8(+) T cells from animals that were administered IFN-lambda 3 showed substantially increased cytotoxic responses as gauged by CD107a and granzyme B coexpression as well as perforin release. Moreover, CD8(+) T cells isolated from the mesenteric lymph nodes (MLN) of animals receiving IFN-lambda 3 loaded significant amounts of granzyme B upon extended antigenic stimulation and induced significantly more granzyme B-mediated cell death of peptide pulsed targets. These data suggest that IFN-lambda 3 is a potent effector of the immune system with special emphasis on CD8(+) T-cell killing functions which warrants further study as a possible immunoadjuvant.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Panyupa
authors.initials: P
authors.lastname: Pankhong
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Kendra
authors.initials: K
authors.lastname: Talbott
authors.forename: Roberta
authors.initials: R
authors.lastname: Toporovski
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D053804:Granzymes / Q000378:metabolism*; D007372:Interferons / Q000494:pharmacology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008251:Macaca; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D007372:Interferons; D053804:Granzymes