Characterization of follicular T helper cells and donor-specific T helper cells in renal transplant patients with de novo donor-specific HLA-antibodies

Characterization of follicular T helper cells and donor-specific T helper cells in renal transplant patients with de novo donor-specific HLA-antibodies

Copyright © 2021 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 226(2021) vom: 07. Mai, Seite 108698
1. Verfasser: Subburayalu, Julien (VerfasserIn)
Weitere Verfasser: Dolff, Sebastian, Xu, Shilei, Sun, Ming, Lindemann, Monika, Heinold, Andreas, Heinemann, Falko M, Tervaert, Jan Willem Cohen, Eisenberger, Ute, Korth, Johannes, Brinkhoff, Alexandra, Kribben, Andreas, Witzke, Oliver, Wilde, Benjamin
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2021
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Allospecific T cell reactivity Antibody-mediated rejection Solid organ transplantation T follicular helper cell T follicular regulatory cell de novo donor-specific HLA-antibodies Antibodies HLA Antigens mehr... Interleukins Receptors, CXCR5 interleukin-21 MKM3CA6LT1
Beschreibung
Zusammenfassung:Copyright © 2021 Elsevier Inc. All rights reserved.
T follicular helper (TFH) cells are a heterogeneous subset of immunocompetent T helper (TH) cells capable of augmenting B cell responses in lymphoid tissues. In transplantation, exposure to allogeneic tissue activates TFH cells increasing the risk of the emergence of de novo donor-specific HLA-antibodies (dnDSA). These can cause antibody-mediated rejection (AMR) and allograft loss. Follicular regulatory T (TFR) cells counteract TFH cell activity. Here, we investigated the implications of TFH and TFR cells on dnDSA formation after renal transplantation (RTX). Considering TFH cells to be CXCR5+ and IL-21+, we found by flow cytometry that patients with dnDSA produced IL-21 more abundantly compared to healthy volunteers. In in vitro alloreactivity assays, patients with dnDSA featured an enhanced alloreactive TH cell pool in response to donor-specific HLA antigens. Besides, longitudinal investigations suggested enhanced alloreactivity shortly after transplantation increasing the risk of dnDSA development. Taken together, in spite of continuous immunosuppression we report a strong IL-21 response in TFH cells and an expanded reservoir of donor-specific memory TH cells in patients with dnDSA. This warrants further investigations if aberrant TFH cell activation may precede the formation of dnDSA promoting AMR
Beschreibung:Date Completed 24.06.2021
Date Revised 24.06.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2021.108698