IL-15 converts human intestinal intraepithelial lymphocytes to CD94 producers of IFN-gamma and IL-10, the latter promoting Fas ligand-mediated cytotoxicity.
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.
Ebert
Ellen C
EC
UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. ebertec@umdnj.edu
D015703:Antigens, CD / Q000032:analysis*; D017209:Apoptosis / Q000276:immunology; D019898:Autocrine Communication / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D053222:Fas Ligand Protein; D025461:Feedback, Physiological / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis*; D008562:Membrane Glycoproteins / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D
D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019409:Interleukin-15; D007376:Interleukin-2; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016753:Interleukin-10; D007371:Interferon-gamma