CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes

Abstract

Significance Refractory celiac disease type II (RCDII) is a severe variant of celiac disease, an autoimmune disorder of the small intestine caused by inflammatory T-cell responses to gluten, a common food protein. Typical of RCDII is the presence of aberrant lymphocytes in the duodenal epithelium, which often give rise to a lethal lymphoma. A single growth factor promoting the expansion of aberrant cells has been identified: epithelial cell-derived IL-15. The experiments described in this paper identify three additional growth factors—TNF, IL-2, and IL-21—produced by gluten-specific T cells. Thus, these findings suggest a potential mechanism for the contribution of gluten-specific T cells to RCDII.