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. 1998 May;42(5):643–649. doi: 10.1136/gut.42.5.643

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

M Carol 1, A Lambrechts 1, A Van Gossum 1, M Libin 1, M Goldman 1, F Mascart-Lemone 1
PMCID: PMC1727108  PMID: 9659157

Abstract

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. 



Keywords: intestinal lymphocytes; ELISPOT; interferon γ; interleukin 4

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Figure 1 .

Figure 1

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Numbers of IFN-γ and/or IL-4 secreting cells per 105 lymphocytes within IEL and LPL cell suspensions obtained from normal human intestinal duodenal and colonic mucosae. Individual results are shown and horizontal bars indicate the medians.


Figure 2 .

Figure 2

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Dot plots from three colour flow cytometric analysis for anti-IFN-γ on CD3+ and on CD8+ or CD8 cells for IEL and LPL. The cells were cultured for four hours with PMA and ionophore A 23187 in the presence of brefeldin A. The fluorescence plots shown are representative of one of three different experiments and cells analysed were gated for CD3+ cells so that results are given as percentage of CD3+ cells. Control isotype was used to differentiate positive from negative immunofluorescence. 


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