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Is there any relationship between IEL and lymphoid follicles in the gastric mucosa?
  1. Catholic University of Rome, Italy
  1. Dr G Cammarota, Policlinico “A Gemelli”, Università Cattolica del Sacro Cuore, Istituto di Medicina Interna e Geriatria, Largo A.Gemelli, 8–00168, Roma, Italy. Email: gcammarota{at}
  1. M HAYAT
  1. Centre for Digestive Diseases
  2. Room 190A Clarendon Wing
  3. General Infirmary at Leeds
  4. Great George Street, Leeds LS1 3EX, UK
  5. Email: mumtaz{at}

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Editor,—The article by Hayatet al (OpenUrlPubMed) reporting the decrease in intraepithelial lymphocytes (IEL) in the gastric mucosa afterHelicobacter pylori eradication is interesting and confirms the suggestion that lymphocytic gastritis could be a manifestation of an atypical host immune response toH pylori. But we would like to ask Dr Hayat and colleagues whether they also investigated the presence of lymphoid follicles in the lamina propria of gastric mucosa of their patients. In fact, mucosa associated lymphoid tissue (MALT), organised in follicles with a germinative centre and B cell reactivity, which structurally resemble Peyer's patches, can develop in the lamina propria afterH pylori infection.1 ,2 Also, the development of these reactive lymphoid follicles may depend on the characteristics of the host and stimuli other thanH pylori. We found lymphoid follicles in the gastric mucosa of 30% of our coeliac patients, of whom only 38% were infected with H pylori,3supporting the hypothesis that the sensitivity of the host to various environmental factors (gliadin, H pylori, viral agents, other factors?) could be essential for the formation of lymphoid agglomerate.

In contrast, the functions of IEL remain a subject of speculation at present. They could be a reaction to abnormal antigen or an indication of abnormal regulatory mechanisms in the host. In some cases these cells have been shown to express CD4 whereas in others, CD8 cells predominate. However, they could play a part in negative regulation of the immune response or, alternatively, in B cell proliferation. Similarly, in the presence of lymphoma, they could represent an overflow of tumour associated T lymphocytes, necessary for the growth of the neoplasia.4 In summary, these IEL may participate in the process of B lymphocyte stimulation where abnormal antigenic stimulation probably plays an important part.

Dr Hayat, what is your opinion about the relationship between IEL and lymphoid follicles in the gastric mucosa?



Editor,—This letter is the third from these authors on the subject of coeliac disease (CD) and gastric lymphoid follicles to be published thus far. Their first letter reported on findings in multiple gastric biopsies from 43 patients with CD.1-1 Thirteen of the 43 (30%) had gastric lymphoid follicles but only five of these had Helicobacter pylori infection, the usual cause of acquired mucosa associated lymphoid tissue (MALT) in the gastric mucosa. Their second letter1-2 speculated on the relationship between lymphocytic gastritis (LG), lymphoid follicles, and H pylori infection. The authors suggested that “the behaviour ofH pylori positive lymphocytic gastritis after antimicrobial treatment should be further investigated”. Our report on such a trial1-3 has elicited a further letter in which Dr Cammarota and Professor Gasbarrini again speculate on the role of IELs in B cell proliferation and argue that such stimulation could lead to follicle formation and ultimately to B cell lymphoma (MALToma).

The key feature of LG is an increase in IELs above a threshold of 25 per 100 epithelial cells, and is therefore analogous to coeliac disease. In CD the most sensitive indicator of a response to treatment is a decline in the density of IELs. Thus we investigated IEL numbers as a measure of response in LG. Follicles are only an occasional histological finding in LG and are not considered to be part of the disease process. We did not therefore investigate the presence of follicles or their relationship to IELs. Indeed, we would go further and claim that there is no rational basis for undertaking such an exercise. B cell proliferation is a consequence of stimulation by activated CD4+ (helper) T lymphocytes mainly through cell-cell contact via the CD40 ligand. Small intestinal IELs are largely made up of CD8+ CD4 T lymphocytes (that is, cytotoxic/suppressor phenotype). Although there are differences between gastric IELs in LG and CD, both the latter populations are largely made up (approximately 70%) of CD8+ cytotoxic/suppressor lymphocytes, with an even greater proportion of IELs expressing a cytoplasmic protein, TIA-1, which is a marker of cytotoxic potential.1-4 Thus few, if any, gastric IELs are of the CD4+ helper T cell phenotype. The role of IELs is not definitely known but there is nothing to suggest that they play a part in follicle formation or control of immunoglobulin synthesis.

Follicles are a prominent feature of H pylori gastritis where IEL counts are uniformly low. Indeed, follicles are particularly prominent in childhood infection where IEL counts are lower than in uninfected controls.1-5

Perhaps Dr Cammarota and Professor Gasbarrini can themselves suggest the mechanism by which IELs stimulate B cell proliferation and test their hypothesis by performing IEL counts and quantitation of IEL subtypes in gastric biopsies with and without follicles from their CD patients?


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