Peripheral CD4CD8 double positive (DP) T cells have been reported to play a role in several autoimmune diseases, virus
infections and cancer. In rheumatoid arthritis (RA), both CD4 and CD8 single positive (SP) T cells are known to be involved in
the pathogenesis, but the role of peripheral CD4CD8 DP T cells has not been investigated in detail. Anti cyclic citrullinated
antibodies (ACPA) positive and ACPA negative RA patients, patients with systemic lupus erythematodes (SLE) and age
matched healthy donors (HD) were enrolled in the analysis. The frequencies and phenotype of DP T cells in PBMC were
investigated. In addition, DP T cells were quantified in biopsies from rheumatoid synovium. After in vitro restimulation, the
cytokine production of DP T cells was investigated in cultures of PBMC. CMV specific cytokine secretion as well as
proliferation was analyzed following antigen specific restimulation after an appropriate culture duration. DP T cells were
found more frequently in RA patients than in healthy controls or patients with SLE. These DP T cells express ab TCRs, are of a
memory phenotype and share features of both CD4 as well as CD8 SP T cells. Importantly, DP T cells were found to also be
present in the rheumatoid synovium. Further characterization of DP T cells from RA patients revealed increased production
of IL-21 and IL-4, implying a possible role as T helper cells. In addition, DP T cells in RA seem to contribute to the
inflammatory process, because they produce significantly more IFNc than counterparts from HD and are increased in CMV+
RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNc), their association with ACPA positive
RA and their presence in the synovium, we suggest an important role of double positive T cells in the pathogenesis of
rheumatoid arthritis.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:12443 |
| Date | January 2014 |
| Creators | Quandt, Dagmar, Wagner, Ulf |
| Contributors | Universität Leipzig, Public Library of Science |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Source | PLoS ONE, March 25, 2014 doi 10.1371/journal.pone.0093293 |
| Rights | info:eu-repo/semantics/openAccess |
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