Increased production of IL-4 by gut T-cell lines from patients with dermatitis herpetiformis compared to patients with isolated gluten-sensitive enteropathy

Dermatitis herpetiformis (DH) and isolated gluten-sensitive enteropathy (GS E) are gluten-sensitive diseases in which ingestion of dietary gluten resul ts in the development of clinical disease. Patients with DH develop cutaneo us IgA deposits and a severe skin disease, but rarely develop gastrointesti nal symptoms. Patients with isolated GSE develop clinically significant gas trointestinal symptoms, but not skin disease or cutaneous IgA deposits. The aim of this study was to investigate the mechanism by which a mucosal immu ne response to the same dietary antigen can result in two distinct clinical phenotypes. T-cell lines were derived from activated T-cells in the small bowel mucosa of five patients with DH and 14 patients with isolated GSE and analyzed for T-cell markers and cytokine production in vitro. T-cell lines from DH and isolated GSE patients produced IFN-gamma after stimulation (me an: DPI = 2619 pg/ml; isolated GSE = 1993 pg/ml; NS). T-cell lines from pat ients with DH, however, produced significantly more IL-4 than the T-cell li nes from patients with isolated GSE (IL-4: DH = 2010 pg/ml; isolated GSE = 235 pg/ml; P < 0.05). Analysis of intracytoplasmic cytokine production by t he T-cell lines showed that T-cell lines from patients with DH were CD4(+) predominant, with a greater proportion of CD4(+)/IL4(+) cells than CD4(+)/I FN-<gamma>(+) cells. In contrast, isolated GSE T-cell lines were predominan tly CD8(+), with an equal proportion of IL-4; and IFN-gamma -positive cells . These studies demonstrate that T cell lines from patients with DH produce significantly more IL-4 than T-cell lines from patients with isolated GSE, while producing similar amounts of IFN-gamma. This difference in cytokine pattern may play an important role in the different clinical manifestations of these two forms of gluten sensitivity.