Immunologic reconstitution is a critical component for successful outcome of
haematopoietic stem cell transplantation. Chemotherapy and pre-transplant conditioning
impairs thymic function leading to delayed T-cell regeneration and the increased risk of
opportunistic infections and leukaemia relapse. Immune reconstitution can be promoted
through administration of common γ-chain cytokines such as IL-2, IL-7 and IL-15.
Prevention of thymic involution achieved by administration of keratinocyte growth
factor, growth hormone and sex hormone inhibition has also been shown to improve
immune reconstitution. Additionally, cell therapy that includes adoptive transfer of ex
vivo generated T-cells or T-cell precursors, T-cells specific for viral or tumour antigens
and, natural killer (NK) cells appears to be a promising therapeutic approach to improve
immune reconstitution after transplantation. Pharmacological modulation of signalling
pathways, such as Wnt and Notch, play an important role during different stages of Tcell
development. Activation of Wnt signalling using small molecule inhibition of
GSK3β was shown to promote post-transplant T-cell regeneration in pre-clinical
models. The use of pharmaceutical agents to accelerate T-cell reconstitution and boost
T-cell-mediated immunity in recipients of haematopoietic stem cell grafts warrants
further investigation.
Keywords: Haematopoeitic stem cell transplantation, immune reconstitution, Tcell,
thymus, Wnt signaling.
