Expansion of peripheral CD8+ CD28- T cells in response to Epstein-Barr virus in patients with rheumatoid arthritis

Klatt, T.; Ouyang, Q.; Flad, T.; Koetter, I.; Bühring, H-Jörg.; Kalbacher, H.; Pawelec, G.; Müller, C.A.

Journal of Rheumatology 32(2): 239-251

2005


ISSN/ISBN: 0315-162X
PMID: 15693083
Document Number: 587833
Objective. To investigate control of Epstein-Barr virus (EBV) infection in rheumatoid arthritis (RA) by comparing the frequency phenotypes and function of peripheral CD8+ EBV-peptide antigen-specific T cells in patients with RA and healthy longterm carriers of EBV. Methods. The frequency of interferon-gamma (IFN-gamma)-producing HLA-A2 or HLA-B8-restricted EBV-reactive CD8+ T cells in peripheral blood mononuclear cells (PBMC) from 49 RA patients and 26 healthy EBV carriers was evaluated in Elispot assays with 12 lytic/latent peptide epitopes. Direct staining with HLA-peptide tetramers containing 3 of these peptides was performed for comparison. The phenotype and function of these T cells was determined by FACS and cytotoxicity testing. Results. IFN-gamma production patterns in Elispot assays revealed that EBV-specific CD8+ T cells were directed predominantly against the lytic epitopes A2/GLC and B8/RAK and to a minor extent to all the other lytic and latent epitopes tested, with no significant differences of the frequencies in patients and controls. However, although similar frequencies of CD8+ T cells stained with A2/GLC or B8/RAK tetramers in both groups, the fraction of A2/GLC or B8/RAK-reactive T cells producing IFN-gamma in response to specific peptide antigen was significantly lower in RA patients than controls. The A2/GLC or B8/RAK tetramer-positive T cells were also substantially enriched in CD28-CD27-T cells of a late-differentiated phenotype in RA patients but not in controls. Conclusion. RA patients show clonal expansion of dysfunctional, terminally differentiated CD8+ EBV-specific T cells in their T cell responses to immunodominant lytic peptide EBV epitopes, which could be a sign of specific impairment of virus-host interactions in RA.

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