T cell receptor repertoire and mitotic responses of lamina propria T lymphocytes in inflammatory bowel disease

Qiao, Liang; Golling, M.; Autschbach, Frank; Schürmann, G.; Meuer, Stefan

doi:10.1111/j.1365-2249.1994.tb06085.x

Cited by 23 publications

(9 citation statements)

References 37 publications

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“…Furthermore, among CD161− LP Teff, a strong, but not quite significant (p=0.055 by unpaired t-test) trend towards greater clonal diversity was seen in samples from patients with UC than without IBD, regardless of whether they came from inflamed segments of colon or not. This argues against a pauciclonal CD4+ Teff population driving inflammation, and thus agrees with early studies of mucosal CD4+ T cell clonality in IBD, using lower resolution technologies than are currently available (5;11;18). …”

Section: Resultssupporting

confidence: 84%

T-cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis

Lord

Chen²,

Thirlby

et al. 2015

Inflammatory Bowel Diseases

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Background & Aims FOXP3+ regulatory T cell (Tregs) prevent inflammation, but are paradoxically increased in ulcerative colitis (UC). Local T cell activation has been hypothesized to account for increased FOXP3 expression in colon lamina propria (LP) T cells. Methods To see if human FOXP3+ LP T cells are an activated fraction of otherwise FOXP3− effector T cells (Teff) and explore their clonal diversity in health and disease, we deep sequenced clonally unique T cell receptor (TCR) hypervariable regions of FOXP3+ and FOXP3− CD4+ T cell subpopulations from inflamed versus non-inflamed colon LP or mesenteric lymph nodes (MLN) of patients with or without UC. Results The clonal diversity of each LP T cell population was no different between patients with versus without UC. Repertoire overlap was only seen between a minority of FOXP3+ and FOXP3− cells, including recently activated CD38+ cells and Th17-like CD161+ Teff, but this repertoire overlap was no different between patients with versus without UC, and was no larger than the overlap between Helios− and Helios+ FOXP3+ cells. Conclusions Thus, at steady state, only a minority of FOXP3+, and particularly Helios+, T cells share a TCR sequence with FOXP3− effector populations in the colon LP, even in UC, revealing distinct clonal origins for LP Tregs and effector T cells in humans.

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Section: Resultssupporting

confidence: 84%

T-cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis

Lord

Chen²,

Thirlby

et al. 2015

Inflammatory Bowel Diseases

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“…Here, we addressed the question whether n‐butyrate contributes to another important feature of intestinal immune homeostasis, namely the low expression of innate immune response receptors (CD11b, CD14, CD16) as well as xCT, the light chain of the cystine/glutamate transporter, as observed on human LPMO . While low expression of innate response receptors impairs recognition of microbial products and hence the initiation of an innate immune response, low xCT expression on LPMO restricts the up‐take of cystine and the production of cysteine by this cell type and thereby contributes to the reduced (cysteine‐dependent) proliferative response of lamina propria T lymphocytes to antigen receptor stimulation .…”

Section: Discussionmentioning

confidence: 99%

Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n‐butyrate

Lasitschka

Giese

Paparella

et al. 2017

Immunity Inflam & Disease

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IntroductionHyporesponsiveness of human lamina propria immune cells to microbial and nutritional antigens represents one important feature of intestinal homeostasis. It is at least partially mediated by low expression of the innate response receptors CD11b, CD14, CD16 as well as the cystine‐glutamate transporter xCT on these cells. Milieu‐specific mechanisms leading to the down‐regulation of these receptors on circulating monocytes, the precursor cells of resident macrophages, are mostly unknown.MethodsHere, we addressed the question whether the short chain fatty acid n‐butyrate, a fermentation product of the mammalian gut microbiota exhibiting histone deacetylase inhibitory activity, is able to modulate expression of these receptors in human circulating monocytes.ResultsExposure to n‐butyrate resulted in the downregulation of CD11b, CD14, as well as CD16 surface expression on circulating monocytes. XCT transcript levels in circulating monocytes were also reduced following exposure to n‐butyrate. Importantly, treatment resulted in the downregulation of protein and gene expression of the transcription factor PU.1, which was shown to be at least partially required for the expression of CD16 in circulating monocytes. PU.1 expression in resident macrophages in situ was observed to be substantially lower in healthy when compared to inflamed colonic mucosa.ConclusionsIn summary, the intestinal microbiota may support symbiosis with the human host organism by n‐butyrate mediated downregulation of protein and gene expression of innate response receptors as well as xCT on circulating monocytes following recruitment to the lamina propria. Downregulation of CD16 gene expression may at least partially be caused at the transcriptional level by the n‐butyrate mediated decrease in expression of the transcription factor PU.1 in circulating monocytes.

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“…In addition there may be a heterogeneity in T cells reactive lo the superantigen [35). Therefore, it remains possible ihat superantigen exposure in the intestine may result in a different TCR repertoire of cytotoxic mucosal T cells, although a recent study suggests that in both normal and CD lamina propria Tceils express a similiar TCR repertoire [36].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

Baca-Estrada

Wong

Croitoru

1995

Clinical and Experimental Immunology

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SUMMARYIn Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimuiated peripheral blood mononuclear celts (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of \3^ T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8 ^ T cells expressing V/38. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V/?8 and V/312 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V/312 subset, SEE stimulation failed to increase cytolytic activity of V/38^ T cells in spile of the expansion of V/38^ Tceils. These results suggest that the changes in cytotoxic function observed in V/38 T cells in Crohn's patients may reflect previous exposure to a V/58-seIective superantigen.

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T cell receptor repertoire and mitotic responses of lamina propria T lymphocytes in inflammatory bowel disease

Cited by 23 publications

References 37 publications

T-cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis

T-cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis

Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n‐butyrate

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

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