IL-17-producing T cells can augment autoantibody-induced arthritis

Jonathan P. Jacobs, Hsin-Jung Joyce Wu, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Rheumatoid arthritis is a T lymphocyte-mediated disorder, but the precise nature of T cell involvement remains unclear. In the K/BxN mouse model of inflammatory arthritis, T cells initiate disease by providing help to B cells to produce arthritogenic autoantibodies. Here,wehave characterized an additional, nonhumoral role for T cells in promoting autoantibody-induced arthritis. AutoreactiveKRNT cells introduced either by direct transfer or bone marrow transplantation into B-cell-deficient hosts enhanced K/BxN serum-transferred arthritis, an effect that was dependent on expression of the cognate MHC-molecule/peptide complex. The T cell influence was dependent on interleukin (IL)-17; in contrast, standard serum-transferred arthritis, unenhanced by the addition of T cells, was unaffected by IL-17 neutralization. An IL-17-producing population of transferred KRN T cells was identified and found to be supported by the cotransfer of arthritogenic autoantibodies. IL-17-producing KRN T cells were enriched in inflamed joints of K/BxN mice, suggesting either selective recruitment or preferential differentiation. These results demonstrate the potential for autoreactive T cells to play two roles in the development of arthritis, both driving the production of pathogenic autoantibodies and bolstering the subsequent inflammatory cascade dependent on the innate immune system.

Original languageEnglish (US)
Pages (from-to)21789-21794
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number51
DOIs
StatePublished - Dec 22 2009
Externally publishedYes

Fingerprint

Interleukin-17
Autoantibodies
Arthritis
T-Lymphocytes
B-Lymphocytes
Serum
Bone Marrow Transplantation
Immune System
Rheumatoid Arthritis
Joints
Peptides

Keywords

  • Arthritis model
  • Inflammation
  • Th17 cell

ASJC Scopus subject areas

  • General

Cite this

IL-17-producing T cells can augment autoantibody-induced arthritis. / Jacobs, Jonathan P.; Wu, Hsin-Jung Joyce; Benoist, Christophe; Mathis, Diane.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 51, 22.12.2009, p. 21789-21794.

Research output: Contribution to journalArticle

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