Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches
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- Chidgey, A.P., Seach, N., Dudakov, J. et al. Semin Immunopathol (2008) 30: 457. doi:10.1007/s00281-008-0140-5
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Poor immune recovery is characteristic of bone marrow transplantation and leads to high levels of morbidity and mortality. The primary underlying cause is a compromised thymic function, resulting from age-induced atrophy and further compounded by the damaging effects of cytoablative conditioning regimes on thymic epithelial cells (TEC). Several strategies have been proposed to enhance T cell reconstitution. Some, such as the use of single biological agents, are currently being tested in clinical trials. However, a more rational approach to immune restoration will be to leverage the evolving repertoire of new technologies. Specifically, the combined targeting of TEC, thymocytes and peripheral T cells, together with the bone marrow niches, promises a more strategic clinical therapeutic platform.