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Excerpt
Aims: Tolerance within the intestine appears to be maintained actively, with intestinal lymphocytes thought to be maintained in a state of controlled activation. However very little is known about these processes in early life, in particular whether spontaneous cytokine production occurs or whether the lymphocytes are maintained anergic.
Methods: We have investigated small intestinal mucosal immune responses in 54 children (aged 4 months-7 years, including 17 with normal histology and 37 with enteropathy) by flow cytometric analysis of single cell cytokine production. We compared gut-derived intraepithelial (IEL) and lamina propria (LPL) lymphocytes with peripheral blood (PBL) lymphocytes. Spontaneous and PMA-stimulated production of TH1 (IL-2, interferon-γ), TH2 (IL-4) and TH3 (TGF-β) cytokines was analysed in CD4+ and CD8+ lymphocytes.
Results: Spontaneous production of all cytokines was low (0-1.4%) in PBL's from both patients and normals, increasing to 10-40% after 4 hours PMA stimulation. By contrast, IEL's and LPL's showed unstimulated production of all cytokines (3-35%) which actually decreased on PMA stimulation. IEL's and LPL's in inflammatory enteropathy and coeliac disease showed increased TH1 and TH2 cytokine production (a TH0 pattern). Substantial non-lymphocyte cytokine production was also seen in both normal and diseased intestine, with the majority of cytokine positivity actually found outside the lymphocyte gates.
Conclusion: Intestinal lymphocytes show a huge increase in spontaneous cytokine production compared to PBL's. In addition we found evidence of many non-lymphocyte cytokine-producing cells, which we are currently characterising. These finding are consistent with the hypothesis of a coordinated continuous immune reaction (physiological inflammation) in the normal small intestine in childhood.
