Rheumatology Advance Access originally published online on February 28, 2003
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Rheumatology 2003; 42: 637-644
© 2003 British Society for Rheumatology
BiP, a putative autoantigen in rheumatoid arthritis, stimulates IL-10-producing CD8-positive T cells from normal individuals
Departments of Rheumatology, GKT School of Medicine, King's College London and Guy's Hospital, London SE1 9RT, UK and
1 Department of Immunology, GKT School of Medicine, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK
Objectives. We have reported that synovial fluid T cells from patients with rheumatoid arthritis (RA) proliferate in response to the endoplasmic reticulum molecular chaperone immunoglobulin binding protein (BiP). The aim of the present work was to clone and define T cells responding to this protein.
Methods. T-cell clones were generated from the peripheral blood of an individual known to respond to BiP by limiting dilution of BiP-stimulated peripheral blood mononuclear cells. T-cell receptor usage of BiP-responsive clones was determined by monoclonal antibody staining followed by flow cytometric analysis. Cytokine production by the BiP-responsive clones was determined by analysis of post-stimulation supernatants by ELISA. Additional phenotyping was performed by flow cytometry.
Results. Of 49 clones isolated, six were shown to proliferate in response to BiP. Proliferation was low but consistent. One clone expressed CD4 and five were CD8-positive. Three clones, all CD8+, grew strongly and were investigated further. T-cell receptor usage was determined in two clones (Vß 7.1 and Vß 12); the Vß element of the remaining clone was not recognized by the panel of antibodies used. All three clones produced interleukin 10 (IL-10) (80–380 pg/ml) and two of them produced IL-4 (10–80 pg/ml) and IL-5 (>5000 pg/ml). One clone produced both IL-10 and interferon 
(>5000 pg/ml). Additional phenotyping of these clones showed them to express CD25, CD28, CD80 and 86 but not CD56 or 57. One clone constitutively expressed CTLA-4 cytoplasmically.
Conclusions. This study demonstrates that a population of CD8+ T cells with the cytokine profile of Tc2 cells can be stimulated by the chaperone BiP. These cells may perform a regulatory role in the normal response to inflammation. The increase in response to this antigen in the synovial joint in RA may indicate an attempt to regulate the ongoing inflammation.
KEY WORDS: Heat shock protein, CD8, IL-10.
Correspondence to: M. Bodman-Smith, Guy's Hospital, London, SE1 9RT, UK. E-mail: mark.bodman-smith{at}kcl.ac.uk