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.

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