Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat

Jens Holmberg, Jonatan Tuncel, Hisakata Yamada, Shemin Lu, Peter Olofsson, Rikard Holmdahl

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Abstract

Pristane-induced arthritis (PIA) in rats, a model for rheumatoid arthritis (RA), is a T cell-dependent disease. However, pristane itself is a lipid and unable to form a stable complex with a MHC class II molecule. Therefore, the specificity and function of the T cells in PIA are as unclear as in rheumatoid arthritis. In this study, we show that activated CD4+ αβT cells, which target peripheral joints, transfer PIA. The pristane-primed T cells are of oligo or polyclonal origin as determined by their arthritogenicity after stimulation with several mitogenic anti-TCRVβ and anti-TCRV α mAbs. Arthritogenic cells secreted IFN-γ and TNF-α (but not IL-4) when stimulated with Con A in vitro, and pretreatments of recipient rats with either anti-IFN-γ or a recombinant TNF-α receptor before transfer ameliorated arthritis development. Most importantly, we show that these T cells are MHC class II restricted, because treatment with Abs against either DQ or DR molecules ameliorates arthritis development. The MHC class II restriction was confirmed by transferring donor T cells to irradiated recipients that were syngenic, semiallogenic, or allogenic to MHC class II molecules, in which only syngenic and semiallogenic recipients developed arthritis. These data suggest that the in vivo administration of a non-antigenic adjuvant, like pristane, activates CD4+ αβT cells that are MHC class II restricted and arthritogenic.

Original languageEnglish
Pages (from-to)1172-1179
Number of pages8
JournalJournal of Immunology
Volume176
Issue number2
DOIs
Publication statusPublished - Jan 15 2006

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Arthritis
T-Lymphocytes
Rheumatoid Arthritis
T-Cell Antigen Receptor Specificity
Tumor Necrosis Factor Receptors
Interleukin-4
pristane
Joints
Lipids

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat. / Holmberg, Jens; Tuncel, Jonatan; Yamada, Hisakata; Lu, Shemin; Olofsson, Peter; Holmdahl, Rikard.

In: Journal of Immunology, Vol. 176, No. 2, 15.01.2006, p. 1172-1179.

Research output: Contribution to journalArticle

Holmberg, Jens ; Tuncel, Jonatan ; Yamada, Hisakata ; Lu, Shemin ; Olofsson, Peter ; Holmdahl, Rikard. / Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat. In: Journal of Immunology. 2006 ; Vol. 176, No. 2. pp. 1172-1179.
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