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Aberrant extrathymi...
Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa : a risk factor for coeliac disease?
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- Bas, A (author)
- Umeå universitet,Immunologi/immunkemi
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- Forsberg, G (author)
- Umeå universitet,Immunologi/immunkemi,Pediatrik
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- Sjöberg, Veronika (author)
- Umeå universitet,Immunologi/immunkemi,Hammarström
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- Hammarström, Sten (author)
- Umeå universitet,Immunologi/immunkemi,Hammarström
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- Hernell, Olle (author)
- Umeå universitet,Pediatrik
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- Hammarström, Marie-Louise (author)
- Umeå universitet,Immunologi/immunkemi,Hammarström
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(creator_code:org_t)
- 2008-02-25
- 2009
- English.
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 58:2, s. 189-195
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https://gut.bmj.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- BACKGROUND: Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. AIM: To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten.METHODS: Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT alpha-chain (preTalpha) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry.RESULTS: In controls, the RAG1-1A/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR(+)) and immature (CD2(+)CD7(+)TCR(-)) IELs ( approximately 8 mRNA copies/18S rRNA U). PreTalpha was expressed almost exclusively in CD2(+)CD7(+)TCR(-) IELs ( approximately 40 mRNA copies/18S rRNA U). By contrast, RAG1 and preTalpha mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values <0.01 for mature and <0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p<0.001).CONCLUSIONS: Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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