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- Title
IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques.
- Authors
Morrow, Matthew P; Yan, Jian; Pankhong, Panyupa; Shedlock, Devon J; Lewis, Mark G; Talbott, Kendra; Toporovski, Roberta; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B
- 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.
- Publication
Molecular therapy : the journal of the American Society of Gene Therapy, 2010, Vol 18, Issue 9, p1714
- ISSN
1525-0024
- Publication type
Journal Article
- DOI
10.1038/mt.2010.118