IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques

Mol Ther. 2010 Sep;18(9):1714-23. doi: 10.1038/mt.2010.118. Epub 2010 Jun 22.


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 types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Granzymes / metabolism*
  • Interferons / pharmacology*
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Macaca
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / metabolism*


  • Lysosomal-Associated Membrane Protein 1
  • Interferons
  • Granzymes