Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Background —Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. Aims —To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. Patients —Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. Methods —Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). Results —The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4 + cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4. Conclusions —Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.