The human chaperone BiP stimulates interleukin(IL)-10 producing CD8 T cells: implications for rheumatoid arthritis

Introduction

Rheumatoid Arthritis (RA) is the most common, crippling autoimmune disease, affecting between 0.3 and 3% of the population. Our laboratory has implicated the human chaperone, BiP, in the disease process.

Aims

This study was aimed at dissecting the T cell response to BiP.

Methods

T cell clones from normal individuals shown to respond to BiP were generated. The specificity of the clones was determined and the clonality determined by staining for the Vβ region of the T cell receptor. Supernatants were taken from the clones and control cells after stimulation with phytohaemagglutinin and cytokine production determined by ELISA. Additional phenotypic investigation was performed by flow cytometry.

Results

Out of the 6 clones isolated, which responded to BiP, 5 expressed CD8 and 1 CD4. Three clones, all CD8⁺, grew strongly and were investigated further. T cell receptor usage was determined in two clones (Vβ 7.1 and Vβ 12) with the Vβ element of the remaining clone not being recognised by the panel of antibodies used. All three clones produced IL-10 (80–380 pg/ml), with two producing IL-4 (10–80 pg/ml) and IL-5 (>5000 pg/ml). One clone produced both IL-10 and IFNγ (>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 shows 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.