IL‐15 converts human intestinal intraepithelial lymphocytes to CD94+ producers of IFN‐γ and IL‐10, the latter promoting Fas ligand‐mediated cytotoxicity

Abstract

Intestinal intraepithelial lymphocytes (IELs), T-cell receptor alphabeta(+) CD8(+) T cells located between epithelial cells, are thought to contribute to Fas ligand (FL)-mediated epithelial cell death in coeliac disease, a condition characterized by excess interleukin-15 (IL-15). This study evaluates the effects of prolonged IL-15 stimulation on IELs. Human IELs were obtained from jejunal mucosa from gastric bypass operations for morbid obesity and cultured for 3 or 10 days with IL-15. As the culture progressed, an increasing number of IELs became CD94(+) and produced massive quantities of interferon-gamma (IFN-gamma) and IL-10. There was a steady rate of transcription with no feedback regulation. Few chronically activated IELs produced IL-2, IL-4, or tumour necrosis factor-alpha (TauNuF-alpha). To determine whether the accumulation of IL-10 affected IEL functions, endogenous IL-10 was neutralized by antibody during culture with IL-15. This manipulation reduced expression of CD94, NKG2D, and FL as well as FL-mediated killing of Jurkat cells by IELs. It did not affect perforin or TNF-alpha expression or the associated cytotoxic activities. This study shows that IL-15 induces the development of CD94(+) IELs containing IFN-gamma and IL-10, and that endogenous IL-10 promotes FL-mediated cytotoxicity.