Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives.
Hemopoietic stem cell transplantation (HSCT) is a standard procedure for treatment of malignant and non-malignant hematological diseases. HSCT donors include HLA-identical siblings, matched or mismatched unrelated donors and haploidentical related donors. Graft-versus-host disease (GvHD), mediated by donor alloreactive T-cells in the graft, can be triggered by minor histocompatibility antigens in HLA-identical pairs, by alleles at loci not considered for MUD-matching or by the mismatched haplotype in haplo-HSCT. Therefore, removal of donor T-cells, that contain the alloreactive precursors, is required, but T-cell depletion associates with opportunistic infections and with reduced graft-versus-leukemia effect. Selective T-cell depletion strategies have been introduced, like removal of αβ T-lymphocytes and of naive T-cells, two subsets including the alloreactive precursors, but the ultimate goal is specific removal of alloreactive T-cells. Here we review the different approaches to deplete alloreactive T-cells only and discuss pros and cons, specificity, efficiency and efficacy. Combinations of different methods and innovative approaches are also proposed for depleting specific alloreactive T-cells with high efficiency.
['Li Pira|Giuseppina|G|', 'Di Cecca|Stefano|S|', 'Montanari|Mauro|M|', 'Moretta|Lorenzo|L|', 'Manca|Fabrizio|F|']
D006086:Graft vs Host Disease D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D013601:T-Lymphocytes D019172:Transplantation Conditioning
Alloreactive T-cells Hemopoietic stem cell transplantation Graft-versus-host disease Allodepletion Cell manipulation T-cell activation