Dataset Information

Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease.

ABSTRACT: Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-? and -? genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined. Persistence of the same clonotypes was seen in both compartments over decades, with up to 53% overlap between samples obtained 16 to 28 years apart. Further, we observed that the recall response following oral gluten challenge was dominated by preexisting CD4+ T cell clonotypes. Public features were frequent among gluten-specific T cells, as 10% of TCR-?, TCR-?, or paired TCR-?? amino acid sequences of total 1813 TCRs generated from 17 patients were observed in 2 or more patients. In established celiac disease, the T cell clonotypes that recognize gluten are persistent for decades, making up fixed repertoires that prevalently exhibit public features. These T cells represent an attractive therapeutic target.

SUBMITTER: Risnes LF

PROVIDER: S-EPMC5983310 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease.

Risnes Louise F LF Christophersen Asbjørn A Dahal-Koirala Shiva S Neumann Ralf S RS Sandve Geir K GK Sarna Vikas K VK Lundin Knut Ea KE Qiao Shuo-Wang SW Sollid Ludvig M LM

The Journal of clinical investigation 20180514 6

Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gu ...[more]

PMID: 29757191

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Project description:BackgroundMulti-level fission-fusion societies, characteristic of a number of large brained mammal species including some primates, cetaceans and elephants, are among the most complex and cognitively demanding animal social systems. Many free-ranging populations of these highly social mammals already face severe human disturbance, which is set to accelerate with projected anthropogenic environmental change. Despite this, our understanding of how such disruption affects core aspects of social functioning is still very limited.ResultsWe now use novel playback experiments to assess decision-making abilities integral to operating successfully within complex societies, and provide the first systematic evidence that fundamental social skills may be significantly impaired by anthropogenic disruption. African elephants (Loxodonta africana) that had experienced separation from family members and translocation during culling operations decades previously performed poorly on systematic tests of their social knowledge, failing to distinguish between callers on the basis of social familiarity. Moreover, elephants from the disrupted population showed no evidence of discriminating between callers when age-related cues simulated individuals on an increasing scale of social dominance, in sharp contrast to the undisturbed population where this core social ability was well developed.ConclusionsKey decision-making abilities that are fundamental to living in complex societies could be significantly altered in the long-term through exposure to severely disruptive events (e.g. culling and translocation). There is an assumption that wildlife responds to increasing pressure from human societies only in terms of demography, however our study demonstrates that the effects may be considerably more pervasive. These findings highlight the potential long-term negative consequences of acute social disruption in cognitively advanced species that live in close-knit kin-based societies, and alter our perspective on the health and functioning of populations that have been subjected to anthropogenic disturbance.

Dataset Information

Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease.

Publications

Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease.

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