title: IL-17-producing T cells can augment autoantibody-induced arthritis.
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, we have characterized an additional, nonhumoral role for T cells in promoting autoantibody-induced arthritis. Autoreactive KRN T 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.
authors: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Jonathan P
authors: JP
authors: Jacobs
authors: Hsin-Jung
authors: HJ
authors: Wu
authors: Christophe
authors: C
authors: Benoist
authors: Diane
authors: D
authors: Mathis
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001769:Blood; D002454:Cell Differentiation; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17