Reconstitution of the immune system after hematopoietic stem cell transplantation in humans

Abstract

Hematopoietic stem cell transplantation is associated with a severe immune deficiency. As a result, the patient is at high risk of infections. Innate immunity, including epithelial barriers, monocytes, granulocytes, and NK cells recovers within weeks after transplantation. By contrast, adaptive immunity recovers much slower. B- and T-cell counts normalize during the first months after transplantation, but in particular, T-cell immunity may remain impaired for years. During the last decade, much of the underlying mechanisms have been identified. These insights may provide new therapies to accelerate recovery.

Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT

“…24,29 The signature of the patients that controlled their CMV reactivation was a polyfunctional response of 'master' CD8 þ T-cells that produce IFNg and IL2 at the same time. Serostatus of donor and recipient impacted on the control of CMV reactivation as summarized previously, 8 but analysis of other clinical factors such as time post transplant, GVHD and others (Table 1) showed no impact on the control of CMV. Thus, we confirmed and extended the findings of Lilleri et al, 30 who reported a relationship between the dual IFNg/IL2 producing T-cells and protection from CMV reactivation in a smaller group of patients.…”

“…Although the T-cell counts recover much earlier by peripheral expansion, the patients suffer from frequent infections, demonstrating the inadequate function of the T-cells. 8 Current treatment strategies involve prophylactic or pre-emptive antiviral treatment. However, both of these approaches lead to significant overtreatment.…”

Plasma levels of IL-7 and IL-15 after reduced intensity conditioned allo-SCT and relationship to acute GVHD

“…4,5 During HPE, naı¨ve T cells are gradually induced to acquire a memory-like phenotype and heightened functions, which can promote antimalignant effects, but also tissue-damaging alloresponses. 6 The homeostatic cytokines IL-7 and IL-15 are essential driving forces for HPE.…”

Torque teno virus in patients undergoing allogeneic hematopoietic stem cell transplantation for hematological malignancies

“…Patients were transplanted for AML (n = 58), ALL (n = 15), myelodysplastic syndrome (MDS) (12), non-Hodgkin lymphoma (NHL) (10), myeloproliferative syndrome (MPS) (6), multiple myeloma (9), HL (5), CML (3), CLL (1), myelodysplastic/ myeloproliferative syndrome (MDPS) (1) or acute plasmacytoid dendritic leukemia. 1 Further details such as (disease) status at transplant or other parameters with a potential impact on the patient's immunity are shown in the Table 1.…”

“…1 The synergy of transplant conditioning and allogeneic effect of the graft will destroy the patient's immune system and in particular antiviral immunity may be impeded for a substantial period of time. Moreover, many patients may already have slumbering viral infections at transplant because the disease and its treatment have weakened their immune system.…”