Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

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Abstract
SUMMARY: In Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of Vβ8 T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8+ T cells expressing Vβ8. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of Vβ8 and Vβ12 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the Vβ12 subset, SEE stimulation failed to increase cytolytic activity of Vβ8+ T cells in spite of the expansion of Vβ8+ T cells. These results suggest that the changes in cytotoxic function observed in Vβ8 T cells in Crohn's patients may reflect previous exposure to a Vβ8-selective superantigen.