T cell-monocyte interactions regulate epithelial physiology in a co-culture model of inflammation. McKay, Derek M., Kenneth Croitoru, and Mary H. Perdue. Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada
APStracts 2:0299C, 1995.
We have examined the effect of T cell activation, +/- monocytes, on epithelial electrolyte transport and barrier functions. Confluent monolayers of human T84 epithelial cells were co-cultured (1-3 days) with peripheral blood mononuclear cells (PBM) or T cells activated by anti-CD3 antibody. Monolayers were then mounted in Ussing chambers and changes in ion transport (indicated by short-circuit current, Isc) and barrier (indicated by resistance and radiolabelled probe fluxes) functions were assessed. Co-culture with activated PBM or conditioned media from these cells altered the transport (decreased Isc responses to carbachol and forskolin) and barrier (decreased resistance and increased fluxes of 3H-mannitol and 51Cr-EDTA) properties of T84 monolayers. In contrast, co-culture with equal numbers of T cells activated in the absence of monocytes did not significantly affect epithelial physiology. Monocytes treated with conditioned media from activated T cells evoked epithelial abnormalities similar to those caused by culture with activated PBM. Total correction of epithelial abnormalities was achieved only by treating T cell conditioned media with anti-IFN before addition to monocytes, as well as addition of anti-TNF[alpha] to the co-culture. Exogenous recombinant IFN and TNF[alpha] added to T84 monolayers did not mimic the physiological changes induced by immune cells; addition of these cytokines to monocytes did reproduce the effects. We conclude that T cell-derived IFN activates monocytes to release TNF[alpha] and other soluble mediators, resulting in epithelial dysfunction. 

Received 19 April 1995; accepted in final form 7 August 195.
APS Manuscript Number C216-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.