T cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles Full Text
Arthritis Research & Therapy, 05/24/2012
Law SC et al. – Pro–inflammatory cytokines were produced by CD4+ T cells in shared epitope (SE)+ individuals in response to citrullinated self–epitopes, of which citrullinated aggrecan was most immunogenic. The data suggest that pro–inflammatory T cell responses towards citrullinated self–epitopes precede the development of Anti–citrullinated peptide antibodies (ACPA), but that the T cell response matures with development of rheumatoid arthritis (RA).
Methods- The authors compared T cell proliferative and cytokines responses to citrullinated and native type II collagen 1237–1249, vimentin 66–78, aggrecan 84–103 and fibrinogen 79–91 in 4 SE+ healthy controls, and in 13 RA patients with disease for <1 or at least 4 years.
- Cytokine–producing cells were stained after incubation with peptide in the presence of Brefeldin–A.
- Although proliferative responses were low, IL–6, IFN– and TNF were secreted by CD4+ T cells of SE+ RA patients and healthy controls, in response to citrullinated peptides.
- Patients with early RA were more likely to produce IL–6 in response to no epitope or to citrullinated aggrecan alone, while patients with longstanding RA were more likely to produce IL–6 to multiple epitopes.
- Cytokine–producing CD4+ T cells included CD45RO+ and CD45RO– and CD28+ and CD28– subsets in RA patients.
