Tumour necrosis factor-α enhances intraepithelial lymphocyte proliferation and migration

Abstract

Background—Tumour necrosis factor α (TNF-α) is a proinflammatory cytokine found in abundance in diseased intestine.Aims—The T cell production of TNF-α and the impact of this cytokine on intestinal T cell proliferation, migration, and cytotoxicity were studied.Methods—Intestinal lymphocytes from normal jejunum were used. TNF-α production in culture supernates was measured by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was measured using 3H thymidine uptake; migration, using transwell chambers; and cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay.Results—TNF-α was produced mainly by the CD8+ T cells in the intraepithelial lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF-α (1 ng/ml or greater) augmented proliferation of IEL in response to interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that did not involve IL-2 production or receptor generation. Conversely, antibody to TNF-α reduced IEL proliferation in response to IL-2 or IL-7. TNF-α also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous migration). TNF-α had no effect on lymphokine activated killer cell activity.Conclusions—TNF-α increases the proliferation and migration of IEL, which may expand their number in the epithelium.