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CD8+ T Cell Profiles in Patients With Rheumatoid Arthritis and Their Relationship to Disease Activity
Author(s) -
Carvalheiro Helena,
Duarte Cátia,
SilvaCardoso Sandra,
da Silva José A. P.,
SoutoCarneiro M. Margarida
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38941
Subject(s) - cd8 , cytotoxic t cell , proinflammatory cytokine , immunology , cytokine , tumor necrosis factor alpha , t cell , rheumatoid arthritis , synovial fluid , medicine , flow cytometry , biology , inflammation , immune system , pathology , in vitro , biochemistry , alternative medicine , osteoarthritis
Objective CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their role in disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8+ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA. Methods CD8+ T cell phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex‐ and age‐matched healthy controls. Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines, and proteolytic enzymes in CD8+ T cells was evaluated using flow cytometry. Results PB CD8+ T cells from RA patients with active disease exhibited an effector (CD27−CD62L−) phenotype ( P = 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor α [TNFα], interferon‐γ [IFNγ], interleukin‐6 [IL‐6], IL‐17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 ( P < 0.001), but lower cytokine production was observed. SF CD8+ T cells from RA patients expressed more robust effector memory (CD27+CD62L−) and activated (CD69+) profiles compared to the T cell subsets in paired PB samples. Production of cytokines (IL‐6, IL‐17A, and IFNγ) by CD8+ T cells from RA PB was positively correlated within individual donors. Moreover, production of cytokines (TNFα, IFNγ, and IL‐17A) by CD8+ T cells from RA PB positively correlated with the Disease Activity Score in 28 joints. Conclusion The activation status and proinflammatory potential of CD8+ T cell subsets observed in the RA patients in this study strongly suggest that a phenotype of local and systemic cytotoxic effector T cells plays a role in this disease.