| First Author | Jacobs JP | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 51 | Pages | 21789-94 |
| PubMed ID | 19955422 | Mgi Jnum | J:155519 |
| Mgi Id | MGI:4414680 | Doi | 10.1073/pnas.0912152106 |
| Citation | Jacobs JP, et al. (2009) IL-17-producing T cells can augment autoantibody-induced arthritis. Proc Natl Acad Sci U S A 106(51):21789-94 |
| abstractText | 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. |
