Article Text

PDF
AB0048 CD8+ T cells in rheumatoid arthritis - differences between remission and active disease
  1. H. Carvalheiro1,
  2. S. Silva-Cardoso1,
  3. C. Duarte2,
  4. T. Rodrigues-Sousa1,
  5. D. Antunes1,
  6. J.A.P. da Silva2,
  7. M.M. Souto-Carneiro1
  1. 1Immunology, Center For Neuroscience and Cell Biology
  2. 2Rheumatology, Hospitais da Universidade de Coimbra, Coimbra, Portugal

Abstract

Background For the past years there has been a clear increase in the interest for T cells in autoimmune diseases (1), where it was found that CD8 T cells can have effector or regulatory functions (2,3). Similar findings in rheumatoid arthritis, indicate that CD8 T cells may have either a pro-inflammatory (4) or an anti-inflammatory function in mouse models of inflammatory arthritis (5). One can argue that these results may be the result of two different CD8 T cell subtypes with effector CD8 T cells enhancing and CD8 suppressor T cells down-regulating the disease.

Objectives In the present study, we accessed if there are RA-specific shifts in the CD8 T cell functional subsets, that may shed some light into their role in the pathogenesis of this disease.

Methods A total of 96 RA patients from the Rheumatology Unit of Hospitais da Universidade de Coimbra were enrolled for this study, from which peripheral blood (n=96) and synovial fluids were collected when possible (n=9). The mean age of this cohort is 58 years, ranging from 21 to 86 years. Healthy peripheral blood samples were obtained from a sex and age matched cohort. The RA activity was assessed using the DAS28 disease activity score, ESR, CRP levels and the account of tender and swollen joints. The establishment of remission was achieved by using partly the EULAR criteria for remission, while the active disease was determined by DAS28 score equal or above 3.2.

Results Here we found that CD8 T cells from the peripheral blood are highly activated in RA patients when compared to healthy controls, with a higher expression of CD69 (p<0.001). Effector CD8 T cells are also increased in the peripheral blood of RA patients, which have a higher expression of CD62L- than healthy controls (p<0.001). CD8 T cells from RA patients also present a significantly higher percentage of intracellular pro-inflammatory cytokines IFNγ (p<0.001), IL-6 (p=0.025), TNFα (p=0.02) and granzyme B (p=0.025).

Activated CD8 T cells seem to accumulate in the remission state of the disease when compared to the active state (p=0.037). This feature is also observed for effector activated (p<0.001) and effector memory CD8 T cells (p<0.001). Central memory CD8 T cells however, are increased in the periphery of active disease RA patients (p=0.003). The intracellular expression of TNFα is increased in CD8 T cells in remission patients (p=0.034).

The CD8 T cells in the synovial fluid also present a highly activated phenotype, with a nearly 10-fold increase in CD69 expression when compared to the paired peripheral blood (p=0.012). The synovial fluids also appear to be enriched in effector activated (p=0.012) and effector memory (p=0.025) CD8 T cells, as well as a trending increase in pro-inflammatory cytokines and granzyme B.

Conclusions Our results indicate that the cytotoxic function of CD8 T cells appear to be exacerbated in RA, since they have an effector/activated phenotype with an increased production of pro-inflammatory cytokines.

  1. J.J. Inglis et al., Arthritis Res Ther 9, R113 (2007).

  2. H.A. Weiss, J.M. Millward, T. Owens, J Neuroimmunol 191, 79 (Nov, 2007).

  3. S. Pang et al., Eur J Immunol 39, 2716 (Oct, 2009).

  4. B.R. Raposo et al., Arthritis Rheum 62, 2953 (Oct, 2010).

  5. M. Suzuki, C. Konya, J.J. Goronzy, C.M. Weyand, Hum Immunol 69, 781 (Nov, 2008).

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.