Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives.

Abstract

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.

• Authors: Giuseppina Li Pira, Stefano Di Cecca, Mauro Montanari, Lorenzo Moretta, Fabrizio Manca
• Journal: Blood reviews (Blood Rev) Vol. 30 Issue 4 Pg. 297-307 (07 2016) ISSN: 1532-1681 [Electronic] England
• PMID: 27066851 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Topics

• Graft vs Host Disease (immunology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• T-Lymphocytes (immunology)
• Transplantation Conditioning (adverse effects, methods)