Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches.
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.
Chidgey
Ann P
AP
Monash Immunology and Stem Cell Laboratories, Building 75, STRIP, Monash University, Wellington Rd, Clayton, 3800, Melbourne, Australia. ann.chidgey@med.monash.edu.au
Seach
Natalie
N
Dudakov
Jarrod
J
Hammett
Maree V
MV
Boyd
Richard L
RL
D000818:Animals; D002986:Clinical Trials as Topic; D004847:Epithelial Cells / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects*