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enhances intraepithelial lymphocyte
proliferation and migration
E C Ebert Department of Medicine,
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson
Medical School, One Robert Wood Johnson Place Accepted for publication 26 November 1997 Background Keywords:
CD8 positive T lymphocytes;
tumour necrosis factor;
lymphokine activated killer activity;
chemokinesis, mucosal immunity;
intestinal epithelium
CN 19, New Brunswick, NJ
08903, USA
Tumour necrosis factor 
(TNF-)
is a proinflammatory cytokine found in abundance in diseased intestine.
AimsThe T cell production of TNF- and the
impact of this cytokine on intestinal T cell proliferation, migration,
and cytotoxicity were studied.
MethodsIntestinal lymphocytes from normal
jejunum were used. TNF- 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.
ResultsTNF- 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- (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- reduced IEL proliferation in response to IL-2 or IL-7. TNF-
also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold
over spontaneous migration). TNF- had no effect on lymphokine
activated killer cell activity.
ConclusionsTNF- increases the proliferation
and migration of IEL, which may expand their number in the epithelium.
(GUT 1998;42:650-655)
© 1998 by Gut
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