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Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis

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...

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Autores principales: Quandt, Dagmar, Rothe, Kathrin, Scholz, Roger, Baerwald, Christoph W., Wagner, Ulf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965555/
https://www.ncbi.nlm.nih.gov/pubmed/24667579
http://dx.doi.org/10.1371/journal.pone.0093293
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author Quandt, Dagmar
Rothe, Kathrin
Scholz, Roger
Baerwald, Christoph W.
Wagner, Ulf
author_facet Quandt, Dagmar
Rothe, Kathrin
Scholz, Roger
Baerwald, Christoph W.
Wagner, Ulf
author_sort Quandt, Dagmar
collection PubMed
description 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 αβ 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 IFNγ than counterparts from HD and are increased in CMV+ RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNγ), 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.
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spelling pubmed-39655552014-03-27 Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis Quandt, Dagmar Rothe, Kathrin Scholz, Roger Baerwald, Christoph W. Wagner, Ulf PLoS One Research Article 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 αβ 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 IFNγ than counterparts from HD and are increased in CMV+ RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNγ), 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. Public Library of Science 2014-03-25 /pmc/articles/PMC3965555/ /pubmed/24667579 http://dx.doi.org/10.1371/journal.pone.0093293 Text en © 2014 Quandt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Quandt, Dagmar
Rothe, Kathrin
Scholz, Roger
Baerwald, Christoph W.
Wagner, Ulf
Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title_full Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title_fullStr Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title_full_unstemmed Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title_short Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis
title_sort peripheral cd4cd8 double positive t cells with a distinct helper cytokine profile are increased in rheumatoid arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965555/
https://www.ncbi.nlm.nih.gov/pubmed/24667579
http://dx.doi.org/10.1371/journal.pone.0093293
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