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Cytoreductive conditioning regimens used in the context of allogeneic hematopoietic cell transplantation (HCT) elicit deficits in innate and adaptive immunity, which predispose patients to infections. As such, transplantation outcomes depend vitally on the successful reconstruction of immune competence. Restoration of a normal peripheral T-cell pool after HCT is a slow process that requires the de novo production of naive T cells in a functionally competent thymus. However, there are several challenges to this regenerative process. Most notably, advanced age, the cytotoxic pretransplantation conditioning, and posttransplantation alloreactivity are risk factors for T-cell immune deficiency as they independently interfere with normal thymus function. Here, we discuss preclinical allogeneic HCT models and clinical observations that have contributed to a better understanding of the transplant-related thymic dysfunction. The identification of the cellular and molecular mechanisms that control regular thymopoiesis but are altered in HCT patients is expected to provide the basis for new therapies that improve the regeneration of the adaptive immune system, especially with functionally competent, naive T cells.

Original publication

DOI

10.1182/blood-2011-02-334623

Type

Journal article

Journal

Blood

Publication Date

23/06/2011

Volume

117

Pages

6768 - 6776

Keywords

Animals, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, T-Lymphocytes, Thymus Gland, Transplantation Conditioning, Transplantation, Homologous