Interleukin-7 and hematopoietic stem cell transplantation: beyond the thymus
Allogeneic stem cell transplantation (allo-SCT) has been established as important treatment modality for patients with hematological malignancies, aplastic anemia, and inborn errors of hematopoietic progenitor cells. Nevertheless, major lethal and non-lethal complications still prohibit a full implementation of allo-SCT. Opportunistic infections are considered a frequent and serious complication of allo-SCT due to impaired immune reconstitution following allo-SCT. Delayed recovery of thymus- dependent naive CD4+ T cells, in particular, is associated with significant susceptibility to opportunistic infections and subsequent transplant-related morbidity and mortality. Improvement of thymopoiesis following allo-SCT has become subject of interest. Interleukin-7 (IL-7) has been identified as key regulator of T-cell lymphopoiesis and peripheral homeostatic T-cell expansion. Preclinical evaluation of posttransplant administration of IL-7 has shown effects both on thymic T-cell development and peripheral T- cell expansion. Considerable controversy exists with respect to IL-7 and its effect on alloreactivity. The work as described in this thesis aims to further clarify the immunorestorative capacities of posttransplant IL-7 administration and its role in alloreactivity using experimental murine transplantation models.
|Keywords||TRECs, alloreactivity, hematopoietic stem cell transplantation, interleukin-7, opportunistic infections, regulatory T cell|
|Promotor||J.J. Cornelissen (Jan) , B. Löwenberg (Bob)|
|Publisher||Erasmus University Rotterdam|
|Sponsor||Cornelissen, Prtof. Dr. J.J. (promotor) Löwenberg, Prof. Dr. B. (promotor) Pharmion B.V. Genzyme Nederland Novartis Pharma B.V. Janssen-Cilag B.V. Bristol-Myers Squibb B.V. Beckman Coulter Nederland B.V. Sanofi-Aventis Netherlands B.V.|
Broers, A.E.. (2007, November 28). Interleukin-7 and hematopoietic stem cell transplantation: beyond the thymus. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/10697