Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Holtmeier, Wolfgang; Rowell, D. L.; Nyberg, Annette; Kagnoff, Martin F.

doi:10.1046/j.1365-2249.1997.d01-887.x

Cited by 19 publications

(12 citation statements)

References 42 publications

(75 reference statements)

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“…In the fetal intestine (around 20 wk of gestation), Vδ2 γδ T cells with a limited TCR diversity are the major population in contrast to adult intestine which is enriched for Vδ1 (and Vδ3) γδ T cells with a diverse TRD repertoire (65,70). Some TCR sequences detected in early fetal liver and thymus are shared with those from the fetal intestine suggesting that the latter is inhabited by an early wave of fetal semi-invariant TRDV2 γδ TCRs to be later stepped away by postnatal diverse TRDV1 TCRs (65,99,102,103). This hypothesis could be verified by HTS of the TCR repertoires of fetal and infant/adult intestine-derived γδ T cells.…”

Section: When: Development Of the γδ Tcr Repertoire In Wavesmentioning

confidence: 99%

Innate and adaptive γδ T cells: How, when, and why

Papadopoulou

Sanchez

Vermijlen

2020

Immunological Reviews

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γδ T cells comprise the third cell lineage of lymphocytes that use, like αβ T cells and B cells, V(D)J gene rearrangement with the potential to generate a highly diverse T cell receptor (TCR) repertoire. There is no obvious conservation of γδ T cell subsets (based on TCR repertoire and/or function) between mice and human, leading to the notion that human and mouse γδ T cells are highly different. In this review we focus on human γδ T cells, building on recent studies using highthroughput sequencing to analyze the TCR repertoire in various settings. We make then the comparison with mouse γδ T cell subsets highlighting the similarities and differences and describe the remarkable changes during lifespan of innate and adaptive γδ T cells. Finally, we propose mechanisms contributing to the generation of innate versus adaptive γδ T cells. We conclude that key elements related to the generation of the γδ TCR repertoire and γδ T cell activation/development are conserved between human and mice, highlighting the similarities between these two species.

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Section: When: Development Of the γδ Tcr Repertoire In Wavesmentioning

confidence: 99%

Innate and adaptive γδ T cells: How, when, and why

Papadopoulou

Sanchez

Vermijlen

2020

Immunological Reviews

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“…Consistent with these data is the observation that epithelial supply of IL-15 cytokine plays a crucial role in γδ T-cell control of mucosal inflammation in murine colitis ( 27 ). Similarly, human intestinal Vδ1 + T-cells are significantly expanded in both celiac disease and IBD ( 28 , 29 ), which are characterized by high mucosal levels of the tissue damage-associated cytokine IL-15 ( 30 – 32 ). Intriguingly, patients with celiac disease exhibit upregulated activity of cytotoxic lymphocytes ( 24 ), but a subset of NKG2A + γδ T-cells can reportedly decrease IFNγ expression by cocultured gut αβ T-cells ( 33 ).…”

Section: γδ T-cells Mediate Epithelial Barrier Protectionmentioning

confidence: 99%

Human γδ T-Cell Control of Mucosal Immunity and Inflammation

McCarthy

Eberl

2018

Front. Immunol.

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Human γδ T-cells include some of the most common “antigen-specific” cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes. These unique functional attributes and lack of MHC restriction have prompted considerable interest in therapeutic targeting of γδ T-cells. Indeed, several drugs already in clinical use, including vedolizumab, infliximab, and azathioprine, likely owe their efficacy in part to modulation of γδ T-cell function. Recent clinical trials of Vδ2+ T-cell-selective treatments indicate a good safety profile in human patients, and efficacy is set to increase as more potent/targeted drugs continue to be developed. Key advances will include identifying methods of directing γδ T-cell recruitment to specific tissues to enhance host protection against invading pathogens, or alternatively, retaining these cells in the circulation to limit peripheral inflammation and/or improve responses to blood malignancies. Human γδ T-cell control of mucosal immunity is likely exerted via multiple mechanisms that induce diverse responses in other types of tissue-resident leukocytes. Understanding the microenvironmental signals that regulate these functions will be critical to the development of new γδ T-cell-based therapies.

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“…In previous studies we have shown that the TCR δ repertoire in the adult human intestine is oligoclonal and is unique in each individual (22, 23). This was also the case in patients with active celiac disease (29). Furthermore, similar data were obtained from normal skin (24), and the TCR δ repertoire from peripheral γδ T cells were also restricted but distinct from those in the intestine or the skin (22, 27).…”

Section: Discussionmentioning

confidence: 53%

Distinct TCR δ repertoires are present in the cutaneous lesions and inflamed duodenum of patients with dermatitis herpetiformis

Holtmeier¹,

Pfänder²,

Zollner

et al. 2002

Experimental Dermatology

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Intraepithelial gammadelta T cells are increased in the inflamed small bowel and are also found in increased numbers in cutaneous lesions from patients with dermatitis herpetiformis (DH). Thus, these cells might play an important role in the pathogenesis of the disease. We investigated the T-cell receptor (TCR) delta repertoire in involved and non-involved skin and compared it with the TCR delta repertoire of the inflamed duodenum and peripheral blood of the same patients. An identical TCR delta repertoire in the small bowel and in the cutaneous lesions would suggest a migration of antigen-specific gammadelta T cells from the intestine to the skin which cross-react with cutaneous antigens. T-cell receptor DV1-DV3 transcripts were amplified by reverse transcriptase (RT)-PCR and analyzed by complementarity determining region 3 (CDR3) size spectratyping and nucleotide sequencing. Our results indicate that the cutaneous TCR delta repertoires were oligoclonal and identical dominant gammadelta T-cell clones were present in the involved and non-involved skin. Furthermore, the TCR delta repertoire of the skin was distinct from that in the small bowel. The peripheral blood exhibited a restricted TCR delta repertoire, which differed from that in the intestine and skin. Thus, cutaneous gammadelta T cells are not specifically expanded within the involved skin and are unlikely to be derived from the inflamed duodenum.

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Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Cited by 19 publications

References 42 publications

Innate and adaptive γδ T cells: How, when, and why

Innate and adaptive γδ T cells: How, when, and why

Human γδ T-Cell Control of Mucosal Immunity and Inflammation

Distinct TCR δ repertoires are present in the cutaneous lesions and inflamed duodenum of patients with dermatitis herpetiformis

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