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Background: De novo donor-specific antibody (dnDSA) generation and acute rejection (AR) are the main factors affecting long-term graft survival. This study aims to investigate human leukocyte antigen (HLA) eplet mismatching (MM), delayed graft function (DGF), and tacrolimus (TAC) trough levels on the occurrence of dnDSA and AR in the early stages after kidney transplantation (KT). Methods: This retrospective study included 526 cases of deceased donation KT. The effects of DGF, HLA eplet MM, and TAC trough levels on dnDSA and AR occurrence were analyzed with logistic regression analysis. Results: Multivariate logistic regression analysis showed the independent risk factor of dnDSA generation was HLA B eplet MM (OR: 1.201. 95% CI: 1.007-1.431, P 0.041). The independent risk factors of AR occurrence include DGF (OR: 4.045, 95% CI: 1.047-15.626, P 0.043), HLA B eplet MM (OR: 1.090, 95% CI: 1.000-1.187, P = 0.050), and TAC trough levels at 12 months (OR: 0.750, 95% CI: 565-0.997, P - 0.048). HLA B eplet MM combined with DGF and TAC trough levels at 12 months increased the predictive value of dnDSA (AUC 0.735) and AR (AUC 0.730) occurrence. HLA B eplet MM > 9 and TAC trough levels below 5.95 ng/mL at 12 months could increase the risk of early AR occurrence. Conclusions: HLA B eplet MM, DGF, and TAC trough levels at 12 months after KT could affect the occurrence of dnDSA and AR in the early stage of KT. [ABSTRACT FROM AUTHOR]

Indoleamine 2, 3-dioxygenase (IDO) is an intracellular hemeprotein enzyme which catalyses the essential amino acid tryptophan. Accumulating evidence has demonstrated that tryptophan depletion and its toxic metabolites expression in tissue microenvironment can suppress local allogeneic T cell proliferation and activation. Ever since the discovery that IDO was involved in the maintenance of fetal-maternal tolerance. numerous studies have confirmed that IDO is a potent regulator of immune cell function, Importantly, LDO+dendritic cells (DCs) might interact with regulatory T cells (Tregs) to form an immunomodulatory network to promote immune tolerance induction. Moreover, it has been reported that overexpression of IDO in transplanted organs can prolong allograft survival, suggesting a possible peripheral tolerogenic pathway with important implications in transplantation. However, the underlying mechanism for the beneficial effects of IDO in transplantation remains unclear. In this review, we attempt to summarize our current understandings about IDO as a mediator of immunity in transplantation and provide an overview of IDO as a new paradigm in transplantation. [ABSTRACT FROM AUTHOR]

Immunoglobulin-like transcript 3 (ILT3) belongs to a family of inhibitory receptors with cytoplasmic immunoreceptor tyrosine based inhibitory motifs (ITIMs). Numerous studies have reported that increased ILT3 expression is associated with the tolerogenic properties of antigen-presenting cells (APCs) including dendritic cells (DCs). In this study, human CD34+ hematopoietic stem/progenitor cells (HPSCs) were transduced with self-inactivating lentiviral vector carrying the ILT3 gene, and then induced to differentiate into DCs. Long-term and sustained transgene expression were observed. Importantly, DCs differentiated from ILT3- transduced HPSCs expressed high levels of human ILT3 and acquired strong tolerogenic capacity. This effect was associated with markedly decreased expression of co-stimulatory molecules (CD80, CD86) and down-regulation of NF-κB. Functionally, ILT3high DCs showed a reduced capacity to stimulate allogeneic T cell proliferation and increased the production of CD4+CD25+Foxp3+ T regulatory cells with immunosuppressive activity. These results demonstrate that DCs derived from ILT3-transduced human CD34+HPSCs display tolerogenic properties to induce T regulatory cells in vitro. [ABSTRACT FROM AUTHOR]