Dataset Information

T-cell receptor-? repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.

ABSTRACT: Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T-cell receptor repertoire remains largely unknown. Using next-generation sequencing, the T-cell receptor alpha (TR?) repertoire of naïve and memory CD8⁺ T cells from 25 patients who had received different forms of allogeneic transplantation was analyzed. In parallel, reconstitution of the CD8⁺/CD4⁺ T-cell subsets was mapped using flow cytometry. When comparing the influence of anti-T-cell therapy, a delay in the reconstitution of the naïve CD8⁺ T-cell repertoire was observed in patients who received in vivo T-cell depletion using antithymocyte globulin or post-transplantation cyclophosphamide in case of haploidentical transplantation. Sequencing of the TR? identified a repertoire consisting of more dominant clonotypes (>1% of reads) in these patients at 6 and 18 months post transplantation. When comparing donor and recipient, approximately 50% and approximately 80% of the donors' memory repertoire were later retrieved in the naïve and memory CD8⁺ T-cell receptor repertoire of the recipients, respectively. Although there was a remarkable expansion of single clones observed in the recipients' memory CD8⁺ TR? repertoire, no clear association between graft-versus-host disease or cytomegalovirus infection and T-cell receptor diversity was identified. A lower TR? diversity was observed in recipients of a cytomegalovirus-seropositive donor (P=0.014). These findings suggest that CD8⁺ T-cell reconstitution in transplanted patients is influenced by the use of T-cell depletion or immunosuppression and the donor repertoire.

SUBMITTER: Link-Rachner CS

PROVIDER: S-EPMC6395323 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.

Link-Rachner Cornelia S CS Eugster Anne A Rücker-Braun Elke E Heidenreich Falk F Oelschlägel Uta U Dahl Andreas A Klesse Christian C Kuhn Matthias M Middeke Jan Moritz JM Bornhäuser Martin M Bonifacio Ezio E Schetelig Johannes J

Haematologica 20180927 3

Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T-cell receptor repertoire remains largely unknown. Using next-generation sequencing, the T-cell receptor alpha (TRα) repertoire of naïve and memory CD8<sup>+</sup> T cells from 25 patients who had received different forms of allogeneic transplantation was analyzed. In parallel, rec ...[more]

PMID: 30262565

Similar Datasets

Project description:Infection is a severe complication of allo-HSCT in children, however, the accurate detection of the infection is hard. In this study, we traced the records of 101 pediatric recipients with allo-HSCT to investigate the pathogens of infection, and collected 54 bronchoalveolar lavage fluid, 32 blood, and 15 cerebrospinal fluid samples. In these samples, 87 was with post-transplant infection and 14 without infection. Using the metagenomic next-generation sequencing (mNGS) and traditional pathogen detection, we compared their sensitivity and specificity to detect pathogens of infection. Our results showed that mNGS was more sensitive (89.7%) than conventional pathogen detection (21.8%), with a difference of 67.9% (P < 0.001), However, mNGS was less specific (78.5%) than traditional methods (92.9%), with a difference of 14.4% (P = 0.596). The sensitivity of mNGS for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 91.7, 85.7, and 90.9%, respectively. In contrast, the sensitivity of conventional testing for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 22.9, 21.4, and 18.2%, respectively. There were significant differences in the sensitivity of mNGS and conventional testing in BALF, blood, and CSF samples, with P values of 0.000, 0.000, and 0.002 respectively. Among the patients with pulmonary infection, 11 pathogens were both identified by mNGS and conventional testing, and 33 by mNGS only. The percentage with the mNGS-positive result was 44/48 (91.7%), including viruses (n = 12), bacteria (n = 17), fungi (n = 9) and mixed infections (n = 6). Among the patients diagnosed with fungal pneumonia (n = 9), the most prevalent pathogenic fungi were Pneumocystis jiroveci (n = 6), which were also detected in 4 patients with mixed infectious pneumonia. In the 28 blood specimens of patients with bloodstream infections or viremia, five patients were positive by both mNGS and conventional testing, 19 were positive by mNGS, and 1 was positive by traditional testing only. The percentage with the mNGS-positive results was 24/28 (85.7%), including viruses (n = 12), bacteria (n = 4), fungi (n = 3), and mixed infections (n = 5). Of the 15 CSF specimens enrolled, 11 patients were eventually diagnosed with CNS infections. Ten pathogens were identified by mNGS in the 11 patients, including viruses (n = 8), bacteria (n = 1), and fungi (n = 1). These results suggest that mNGS is more sensitive than conventional pathogen detection for diagnosing infections post HSCT in children which may help the clinic diagnosis. Pneumocystis jiroveci was the most frequent pathogen of pulmonary infections post-transplant, while viruses were the most common pathogens of CNS infections in allo-HSCT recipients.

Dataset Information

T-cell receptor-? repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.

Publications

T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets