The role of the thymus in allogeneic bone marrow transplantation and the recovery of the peripheral T-cell compartment
- 8 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Seminars in Immunopathology
- Vol. 43 (1), 101-117
- https://doi.org/10.1007/s00281-020-00828-7
Abstract
As the thymus represents the primary site of T-cell development, optimal thymic function is of paramount importance for the successful reconstitution of the adaptive immunity after allogeneic hematopoietic stem cell transplantation. Thymus involutes as part of the aging process and several factors, including previous chemotherapy treatments, conditioning regimen used in preparation to the allograft, occurrence of graft-versus-host disease, and steroid therapy that impair the integrity of the thymus, thus affecting its role in supporting T-cell neogenesis. Although the pathways governing its regeneration are still poorly understood, the thymus has a remarkable capacity to recover its function after damage. Measurement of both recent thymic emigrants and T-cell receptor excision circles is valuable tools to assess thymic output and gain insights on its function. In this review, we will extensively discuss available data on factors regulating thymic function after allogeneic hematopoietic stem cell transplantation, as well as the strategies and therapeutic approaches under investigation to promote thymic reconstitution and accelerate immune recovery in transplanted patients, including the use of cytokines, sex-steroid ablation, precursor T-cells, and thymus bioengineering. Although none of them is routinely used in the clinic, these approaches have the potential to enhance thymic function and immune recovery, not only in patients given an allograft but also in other conditions characterized by immune deficiencies related to a defective function of the thymus.Keywords
Funding Information
- Amy Strelzer Manasevit Research Program
- Italian Association for Cancer Research (My First Grant AIRC)
- Italian Association for Cancer Research (Special Program Metastatic disease: the key unmet need in oncology 5 per mille 2018 Project Code 21147 and Accelerator Award 2017 INCAR)
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN ID 2017 WC8499_004)
- Ministero della Salute (RF-2016-02364388)
- French Government’s Investissement d’Avenir Program
- Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01, ANR-10-LABX-69-01)
- Agence Nationale de la Recherche (Project RANKLthym ANR-19- CE18-0021-02)
- Agence Nationale de la Recherche (Project RANKLthym ANR-19- CE18-0021-02)
- Italian Ministry of Health
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