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T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies

Academic Article
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Overview

authors

  • Lewicki, H.
  • Tishon, A.
  • Homann, D.
  • Mazarguil, H.
  • Laval, F.
  • Asensio, V. C.
  • Campbell, I. L.
  • DeArmond, S.
  • Coon, B.
  • Teng, C.
  • Gairin, J. E.
  • Oldstone, Michael

publication date

  • March 2003

journal

  • Journal of Virology  Journal

abstract

  • CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP(-/-)) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1beta, IFN-gamma-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease. T cells harvested from brains and spleens of scrapie-infected mice were analyzed using a newly identified mouse PrP (mPrP) peptide bearing the canonical binding motifs to major histocompatibility complex (MHC) class I H-2(b) or H-2(d) molecules, appropriate MHC class I tetramers made to include these peptides, and CD4 and CD8 T cells stimulated with 15-mer overlapping peptides covering the whole mPrP. Minimal to modest K(b) tetramer binding of mPrP amino acids (aa) 2 to 9, aa 152 to 160, and aa 232 to 241 was observed, but such tetramer-binding lymphocytes as well as CD4 and CD8 lymphocytes incubated with the full repertoire of mPrP peptides failed to synthesize intracellular gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) cytokines and were unable to lyse PrP(-/-) embryo fibroblasts or macrophages coated with (51)Cr-labeled mPrP peptide. These results suggest that the expression of PrP(sc) in the CNS is associated with release of chemokines and, as shown previously, cytokines that attract and retain PrP-activated T cells and, quite likely, bystander activated T cells that have migrated from the periphery into the CNS. However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-gamma and TNF-alpha expression or release or lytic activity.

subject areas

  • Amino Acid Sequence
  • Animals
  • Brain
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Line
  • Creutzfeldt-Jakob Syndrome
  • H-2 Antigens
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptides
  • PrPSc Proteins
  • Scrapie
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Identity

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.77.6.3799-3808.2003

PubMed ID

  • 12610154
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Additional Document Info

start page

  • 3799

end page

  • 3808

volume

  • 77

issue

  • 6

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