Tolerogenic effect of non-inherited maternal antigens in hematopoietic stem cell transplantation

Major histocompatibility complex antigens that provoke severe transplant reactions are referred to as the human leukocyte antigen (HLA) in human and as the H-2 in mice. Even if the donor and recipient are HLA-identical siblings, graft-versus-host reactions have been linked to differences in the minor histocompatibility antigen. As the chance of finding an HLA-identical sibling donor is only 25%, attention has been focused on using alternative donors. An HLA-mismatched donor with non-inherited maternal antigens (NIMA) is less immunogenic than that with non-inherited paternal antigens, because the contact between the immune systems of the mother and child during pregnancy affects the immune response of the child against NIMA. However, the immunologic effects of developmental exposure to NIMA are heterogeneous, and can be either tolerogenic or immunogenic. We recently have devised a novel method for predicting the tolerogenic effect of NIMA. In this review, we overview the evidence for the existence of the NIMA tolerogenic effect, the possible cellular and molecular basis of the phenomenon, and its utilization in hematopoietic stem cell transplantation. We suggest a future direction for the safe clinical use of this phenomenon, fetomaternal tolerance, in the transplantation field

Increased Level of IFN-γ and IL-4 Spot-Forming Cells on ELISPOT Assay as Biomarkers for Acute Graft-Versus-Host Disease and Concurrent Infections

Acute graft-versus-host disease (aGVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Infections may coexist and in certain circumstances aggravate aGVHD. It was described that type 1 as well as type 2 cytokines are important mediators of aGVHD. We measured spot-forming cells (SFCs) for interferon (IFN)-γ, interleukin (IL)-4, IL-10, and IL-17 in unstimulated peripheral blood from 80 patients with hematological disorders who underwent allogeneic hematopoietic stem cell transplantation by using the enzyme-linked immunospot (ELISPOT) assay that reflects the ongoing in vivo immune status. A serial monitoring showed that both type 1 and type 2 cytokine SFCs were correlated with aGVHD activity. The numbers of IFN-γ and IL-4 SFCs in patients with grade II-IV aGVHD were significantly higher than those in patients with grade 0 and/or I aGVHD. Elevation of IFN-γ and IL-4 SFCs was significantly correlated with the severity of aGVHD, but not with infection itself, e.g., cytomegalovirus infection. Cytokine SFCs are clinically relevant biomarkers for the diagnostic and therapeutic evaluation of aGVHD and concurrent infection