2017
DOI: 10.3390/biomedicines5020033
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T-Cell Manipulation Strategies to Prevent Graft-Versus-Host Disease in Haploidentical Stem Cell Transplantation

Abstract: Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably… Show more

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Cited by 30 publications
(11 citation statements)
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“…In addition, the inhibition of CXCR3 ameliorates GVHD in allo-HSCT mice (46). Activated alloreactive CD8 + T cells upregulate the expression of CX3CR1 and CXCR6 after allo-HSCT (47,48), and these receptors are important for the homing of CD8 + T cells to the liver and intestines. Thus, CXCR6 deficiency or blockade of the CXCR3 and CXCR6 ligands attenuates GVHD (47).…”
Section: Discussionmentioning
confidence: 99%
“…In addition, the inhibition of CXCR3 ameliorates GVHD in allo-HSCT mice (46). Activated alloreactive CD8 + T cells upregulate the expression of CX3CR1 and CXCR6 after allo-HSCT (47,48), and these receptors are important for the homing of CD8 + T cells to the liver and intestines. Thus, CXCR6 deficiency or blockade of the CXCR3 and CXCR6 ligands attenuates GVHD (47).…”
Section: Discussionmentioning
confidence: 99%
“…Immunological outcomes after HSCT are influenced by clinical variables including patient factors (age, indication for transplant, prior treatment, comorbidities), donor type ( 29 , 30 ), stem cell source ( 31 33 ), conditioning regimen ( 34 , 35 ), the use of T cell depletion strategies ( 36 ), and post-transplant pharmacological immunosuppression. Each of these factors has a distinct impact on the post-transplant course and can determine the pace and pattern of immune recovery (Figure 1 ).…”
Section: Immune Reconstitution After Hsctmentioning
confidence: 99%
“…14,15 Hence, more selective T-cell depletion techniques that effectively remove naïve alloreactive T cells but save potentially beneficial donor T-cell subsets have been studied. 16,17 CD45RA-depletion has been shown to preserve diverse donor memory cell populations that may be effective in providing protection against infections and relapse, with little added risk of severe GVHD. [18][19][20][21] Therefore, we recently incorporated CD45RAdepletion into our institutional haploHCT protocols for treatment of patients with hematologic malignancies.…”
Section: Introductionmentioning
confidence: 99%