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

Abstract

SUMMARYIn 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)-stimuiated peripheral blood mononuclear celts (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of \3^ T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8 ^ T cells expressing V/38. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V/?8 and V/312 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V/312 subset, SEE stimulation failed to increase cytolytic activity of V/38^ T cells in spile of the expansion of V/38^ Tceils. These results suggest that the changes in cytotoxic function observed in V/38 T cells in Crohn's patients may reflect previous exposure to a V/58-seIective superantigen.

Metagenomic Characterization of Microbial Communities In Situ Within the Deeper Layers of the Ileum in Crohn’s Disease

“… 10 Superantigens secreted by these strains are potent T-cell mitogens that lead to a massive release of proinflammatory cytokines, 11 and several reports have highlighted the ability of enterotoxigenic strains to trigger intestinal inflammation. 10 , 12 , 13 , 14 These observations suggest that enterotoxigenic strains, coupled with compromised barrier function in intestinal epithelia, may contribute to localized lesions in CD.…”

Repertoire of the αβ T‐cell receptor in the intestine

“…The differences in TCRBV usage, primarily in the CD4 + T‐cell LPL population, were consistent with a specific antigenic immune response (52). This response contrasted with the one that would be observed with a superantigen response, where the same TCRBV would be identified in all individuals (53). Furthermore, the expansions of these CD4 + T cells were greater in the inflamed versus the non‐inflamed CD tissue sites (52, 54).…”

Staphylococcal enterotoxins in the Etiopathogenesis of Mucosal Autoimmunity within the Gastrointestinal Tract

“…Since neither feeder cells nor any exogenous antigens that may modify Vβ gene expression were applied, T cell activation was solely dependent on biopsy-derived endogenous stimulants and the results indicated a prior in vivo exposure to Vβ8-selective superantigens. Indeed, in vitro stimulation of colonic explants from patients with Crohn’s disease or ulcerative colitis with SEB or SEE led to the expansion of T cells expressing Vβ8 and a concomitant inflammatory cytokine release; the response was greater in the inflamed than non-inflamed tissues [ 114 , 115 , 116 ]. Interestingly, the cytotoxic function of Vβ8 + cells seemed to be compromised in Crohn’s disease patients [ 115 ].…”