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Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat an increasing number of congenital and acquired disorders of the haematopoietic system. Even though cytoreductive conditioning regimens vary in intensity, all clinically used protocols invariably cause side effects that compromise transiently or long-term the response of the natural and the adaptive immune systems. However, in the context of the reconstruction of immunity, the generation of naïve T cells constitutes a slow process, and requires a functionally competent thymus. Unfortunately, regular thymic function is frequently suppressed by transplant-related toxicities. Most notably, graft-versus-host disease (GVHD) causes a state of posttransplantation immune deficiency. Here we discuss preclinical allogeneic HSCT models and clinical observations that have contributed to a detailed understanding of the cellular and molecular mechanisms responsible for the thymic dysfunction caused by acute GVHD. An in-depth knowledge of the mechanisms that control regular thymopoiesis and, conversely, affect thymus function is expected to provide the factual basis for the design of innovative therapies to recover T-cell numbers and function following allogeneic HSCT.

Original publication

DOI

10.4414/smw.2010.13051

Type

Journal article

Journal

Swiss Med Wkly

Publication Date

19/07/2010

Volume

140

Keywords

Adaptive Immunity, Animals, Disease Models, Animal, Epithelial Cells, Fibroblast Growth Factor 7, Graft vs Host Disease, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation, Humans, Immunity, Innate, Immunologic Deficiency Syndromes, Lymphocyte Count, Regeneration, T-Lymphocytes, Thymus Gland, Transplantation Conditioning