Tumour necrosis factor-alpha enhances intraepithelial lymphocyte proliferation and migration.
BACKGROUND
Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine found in abundance in diseased intestine.


OBJECTIVE
The T cell production of TNF-alpha 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-alpha 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-alpha 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-alpha (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-alpha reduced IEL proliferation in response to IL-2 or IL-7. TNF-alpha also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous migration). TNF-alpha had no effect on lymphokine activated killer cell activity.


CONCLUSIONS
TNF-alpha increases the proliferation and migration of IEL, which may expand their number in the epithelium.
Ebert
E C
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Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007583:Jejunum / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha