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Nk cell-mediated killing of target cells triggers robust antigen-specific t cell-mediated and humoral responses

Academic Article
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Overview

related to degree

  • Barnes, Michael, Ph.D. in Immunology & Genetics, Scripps Research , Joint graduate program with Oxford University 2004 - 2010

authors

  • Krebs, P.
  • Barnes, Michael
  • Lampe, K.
  • Whitley, K.
  • Bahjat, K. S.
  • Beutler, Bruce
  • Janssen, E.
  • Hoebe, K.

publication date

  • June 2009

journal

  • Blood  Journal

abstract

  • Previous work showed that administration of antigen-expressing apoptotic cells in vivo results in antigen-specific CD8+ T-cell responses independent of Toll-like receptor signaling. We report here that natural killer (NK) cells can serve a function directly upstream of this pathway and initiate robust adaptive immune responses via killing of antigen-expressing target cells. This pathway is highly sensitive, in that administration of as few as 10(4) target cells induced detectable antigen-specific CD8+ T-cell responses. Importantly, NK cell-mediated cytotoxicity of target cells could also induce robust antigen-specific CD4+ T-cell responses, which were critical for subsequent CD8+ T-cell priming and IgG responses. Unlike adaptive immune responses induced by gamma-irradiated cells, the NK-cell pathway required myeloid differentiating factor 88 (MyD88) and Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (Trif) signaling. NK cells have previously been shown to detect and kill pathogen-infected host cells, as well as neoplastic cells and tissue allografts. The present data provide further evidence that they also discharge a strong tie with their relatives in the adaptive immune system. We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development.

subject areas

  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Antibody Specificity
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cytotoxicity, Immunologic
  • H-2 Antigens
  • Immunoglobulin G
  • Immunologic Memory
  • Killer Cells, Natural
  • Listeria monocytogenes
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Myeloid Differentiation Factor 88
  • Ovalbumin
  • Peptide Fragments
  • T-Cell Antigen Receptor Specificity
  • Vaccination
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Identity

PubMed Central ID

  • PMC2710917

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-01-201467

PubMed ID

  • 19406986
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Additional Document Info

start page

  • 6593

end page

  • 6602

volume

  • 113

issue

  • 26

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