- Paper Report
- Open Access
T cell response to hnRNPA2 in patients with rheumatoid arthritis
- Fanny Monneaux1
© Biomed Central Ltd 2002
- Received: 3 September 2002
- Accepted: 12 September 2002
- Published: 19 September 2002
- Rheumatoid arthritis
- T cell response
Rheumatoid arthritis (RA) is systemic joint disease characterized by infiltration of many immune cells such as B and T cells and macrophages in the synovial membrane leading to a chronic inflammatory joint disease. To better understand the role of T cells in the pathogenesis of RA, the authors studied the T cell response against two Ag (hnRNPA2/RA33 and filaggrin (fil)) targeted by Abs of patients with RA. These Ag seem to be specific for RA as Abs to A2/RA33 and Fil are detected in 1/3 and 40-50% of RA patients respectively. Because Abs directed to Fil recognize the citrulinnated form of the protein, T cell responses were studied against both the unmodified and the citrulinnated form of Fil.
PBMC and synovial T cells from RA patients proliferate strongly in response to A2/RA33 (60% vs 20% in controls). In contrast, no difference was found in response to Fil between RA patients and controls. T cell response to A2/RA33 in RA patients is HLA-DR restricted and characterized by a Th1 cytokine profile with high IFN-γ and low IL-4 secretion in both RA and control PBMC, and higher IL-2 production by PBMC of RA patients. T cell lines specific to A2/RA33 were established from PBMC of RA patients and healthy donors. In the term of proliferative response, no significant difference was found between T cell lines from RA patients and those of controls. In contrast, the majority of RA T cell lines are CD4+CD8- with Th1 phenotype, whereas T cell lines generated from healthy donors show heterogeneous phenotype and secrete significantly less IFN-γ than clones from RA patients. Finally, the authors also found that A2/RA33 is abundantly expressed in RA synovial tissues and interestingly, was detected not only in the nucleus but also in the cytoplasm of RA synovial cells. The characterization of autoreactive T cells to A2/RA33 associated with overexpression of a relocalized protein leads the authors to conclude that A2/RA33 may be an important autoAg in RA.
T cell stimulation assays, T cell lines, immunohistochemistry
- Fritsch R, Eselböck D, Skriner K, Jahn-Scmid B, Scheinecker C, Bohle B, Tohidast-Akrad M, Hayer S, Neumüller J, Pinol-Roma S, Smolen JS, Steiner G: Characterization of autoreactive T cells to the autoantigens heterogeneous nuclear ribonucleoprotein A2(RA33) and filaggrin in patients with rheumatoid arthritis. J Immunol. 2002, 169: 1068-1076.PubMedView ArticleGoogle Scholar