Copolymer effects on microglia and T cells in the central nervous system of humanized mice

Zsolt Illes, Joel N H Stern, Derin B. Keskin, Jayagopala Reddy, Celia F. Brosnan, Hanspeter Waldner, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia upregulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-γ, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length γβ and αβ subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVβ2+ MPB85-99-specific transgenic and hVβ2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVβ2- endogenous T cells.

Original languageEnglish (US)
Pages (from-to)3683-3693
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number12
DOIs
StatePublished - Dec 2005
Externally publishedYes

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Microglia
Central Nervous System
T-Lymphocytes
HLA-DR2 Antigen
Granulocyte-Macrophage Colony-Stimulating Factor
Adaptor Protein Complex 1
Transcription Factor AP-1
HLA-DR Antigens
T-Cell Antigen Receptor
Oligonucleotide Array Sequence Analysis
Interleukin-4
Interleukin-10
Dendritic Cells
Anti-Inflammatory Agents
Bone Marrow
myelin basic protein 85-99
Lymphocytes
Amino Acids

Keywords

  • Antigen
  • MHC class II
  • Multimer
  • Suppression/anergy
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

Illes, Z., Stern, J. N. H., Keskin, D. B., Reddy, J., Brosnan, C. F., Waldner, H., ... Strominger, J. L. (2005). Copolymer effects on microglia and T cells in the central nervous system of humanized mice. European Journal of Immunology, 35(12), 3683-3693. https://doi.org/10.1002/eji.200526121

Copolymer effects on microglia and T cells in the central nervous system of humanized mice. / Illes, Zsolt; Stern, Joel N H; Keskin, Derin B.; Reddy, Jayagopala; Brosnan, Celia F.; Waldner, Hanspeter; Santambrogio, Laura; Kuchroo, Vijay K.; Strominger, Jack L.

In: European Journal of Immunology, Vol. 35, No. 12, 12.2005, p. 3683-3693.

Research output: Contribution to journalArticle

Illes, Z, Stern, JNH, Keskin, DB, Reddy, J, Brosnan, CF, Waldner, H, Santambrogio, L, Kuchroo, VK & Strominger, JL 2005, 'Copolymer effects on microglia and T cells in the central nervous system of humanized mice', European Journal of Immunology, vol. 35, no. 12, pp. 3683-3693. https://doi.org/10.1002/eji.200526121
Illes, Zsolt ; Stern, Joel N H ; Keskin, Derin B. ; Reddy, Jayagopala ; Brosnan, Celia F. ; Waldner, Hanspeter ; Santambrogio, Laura ; Kuchroo, Vijay K. ; Strominger, Jack L. / Copolymer effects on microglia and T cells in the central nervous system of humanized mice. In: European Journal of Immunology. 2005 ; Vol. 35, No. 12. pp. 3683-3693.
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AU - Brosnan, Celia F.

AU - Waldner, Hanspeter

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