T-cell receptor-α 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 (TRα) 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 TRα 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+ TRα repertoire, no clear association between graft-versus-host disease or cytomegalovirus infection and T-cell receptor diversity was identified. A lower TRα 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.

• Authors: Cornelia S Link-Rachner, Anne Eugster, Elke Rücker-Braun, Falk Heidenreich, Uta Oelschlägel, Andreas Dahl, Christian Klesse, Matthias Kuhn, Jan Moritz Middeke, Martin Bornhäuser, Ezio Bonifacio, Johannes Schetelig
• Journal: Haematologica (Haematologica) Vol. 104 Issue 3 Pg. 622-631 (03 2019) ISSN: 1592-8721 [Electronic] Italy
• PMID: 30262565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2019 Ferrata Storti Foundation.

Chemical References

• Receptors, Antigen, T-Cell, alpha-beta

Topics

• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Female
• Graft vs Host Disease (etiology)
• Hematopoietic Stem Cell Transplantation
• High-Throughput Nucleotide Sequencing
• Humans
• Immunologic Memory
• Lymphocyte Depletion
• Male
• Receptors, Antigen, T-Cell, alpha-beta (genetics, metabolism)
• T-Lymphocyte Subsets (immunology, metabolism)
• Transplantation, Homologous