Steines, Louisa and Poth, Helen and Schuster, Antonia and Amann, Kerstin and Banas, Bernhard and Bergler, Tobias (2021) Disruption of Tfh:B Cell Interactions Prevents Antibody-Mediated Rejection in a Kidney Transplant Model in Rats: Impact of Calcineurin Inhibitor Dose. FRONTIERS IN IMMUNOLOGY, 12: 657894. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
We aimed to investigate the mechanisms of humoral immune activation in ABMR using a MHC-mismatched rat kidney transplant model. We applied low dose cyclosporine A (loCNI) to allow donor-specific antibody (DSA) formation and rejection and high dose cyclosporine A (hiCNI) for non-rejection. DSA and leukocyte subsets were measured by flow cytometry. Germinal centers (GC), T follicular helper cells (Tfh), plasma cells and interleukin-21 (IL-21) expression were analyzed by immunofluorescence microscopy. Expression of important costimulatory molecules and cytokines was measured by qRT-PCR. Allograft rejection was evaluated by a nephropathologist. We found that DSA formation correlated with GC frequency and expansion, and that GC size was linked to the number of activated Tfh. In hiCNI, GC and activated Tfh were virtually absent, resulting in fewer plasma cells and no DSA or ABMR. Expression of B cell activating T cell cytokine IL-21 was substantially inhibited in hiCNI, but not in loCNI. In addition, hiCNI showed lower expression of ICOS ligand and IL-6, which stimulate Tfh differentiation and maintenance. Overall, Tfh:B cell crosstalk was controlled only by hiCNI treatment, preventing the development of DSA and ABMR. Additional strategies targeting Tfh:B cell interactions are needed for preventing alloantibody formation and ABMR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FOLLICULAR-HELPER-CELLS; DONOR-SPECIFIC ANTIBODY; HLA ANTIBODIES; T-CELLS; B-CELLS; MEMORY; INTERLEUKIN-21; GENERATION; NAIVE; ICOS; antibody-mediated rejection; donor-specific antibodies; kidney transplantation; T follicular helper cells; B cell activation; calcineurin inhibitor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2022 09:23 |
| Last Modified: | 02 Aug 2022 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45991 |
Actions (login required)
 |
View Item |
