Human leukocyte antigen haploidentical hematopoietic stem cell transplantation: indications and tentative outcomes in Japan.
ABSTRACT The stem cell banking system in Japan by the Japan Marrow Donor Program (JMDP) and Japan Cord Blood Bank Network (JCBBN) has provided increased opportunities for patients who might benefit from stem cell transplant from allogeneic sources but who lack human leukocyte antigen (HLA)-matched related donors. Nevertheless, most patients probably do not undergo transplantation because of the absence of suitable stem cell sources. To fulfill this potential need, the outcomes of transplants from HLA-mismatched relatives with or without T-cell depletion were retrospectively analyzed: the rates of engraftment and survival were insufficient in transplants with T-cell depletion, and the actual increase in transplantable donor numbers was small because only a single locus mismatched donor was the realistic choice in those without T-cell depletion. Since prophylaxis with tacrolimus reduced the incidence of grade I-IV acute graft-versus-host disease (GVHD) in HLA class I allele mismatched unrelated donors, we studied transplantation from HLA one haploidentical family donors who showed microchimerism of noninherited maternal antigens, without T-cell depletion but with tacrolimus prophylaxis. The rates of engraftment and survival in this circumstance were similar to those obtained with transplantation from HLA-matched sibling donors.
Article: Tolerance induction or sensitization in mice exposed to noninherited maternal antigens (NIMA).[show abstract] [hide abstract]
ABSTRACT: Developmental exposure to noninherited maternal antigens (NIMA) exerts a tolerizing or sensitizing influence on clinical transplantation in humans and experimental animals. The aim of this study was to determine if strain and gender differences influence the NIMA effect. Six different mouse strain backcross matings of F(1) females with homozygous males ('NIMA backcross') and corresponding control breedings of F1 males with homozygous females were performed. H-2 homozygous offspring underwent heterotopic heart transplantation from fully allogeneic donors expressing noninherited H-2 antigens. A NIMA tolerizing effect on heart allograft outcome was found in three of six breeding models. In all three cases, the tolerizing antigens were from an H-2(d+) strain. The tolerogenic effect was greatest in male as compared with female recipients. Offspring from the three breeding models in which no tolerance was seen, appeared to be sensitized based on poorer graft survival, or enhanced T- or B-cell responses to the noninherited H-2(b or k) antigens. Significantly higher percentages of maternal antigen(+) cells were found in the peripheral blood of tolerant versus nontolerant strains of backcross mice prior to transplant. Our findings imply that transplants are predisposed to tolerance or rejection due to recipient developmental history and immunogenetic background.American Journal of Transplantation 12/2008; 8(11):2307-15. · 6.39 Impact Factor
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ABSTRACT: Exposure to non-inherited maternal antigens (NIMA) has life-long immunological consequences that may result in tolerance or immunity to these antigens. Gaining understanding of the mechanisms behind these NIMA effects will impact many areas of immunology. This review summarizes new discoveries relevant to autoimmunity and organ transplantation regarding exposure to maternal antigens. In light of these studies, as well as unpublished data from our lab, we conclude that the effect of neonatal exposure to maternal antigens has profound impact on clinical and experimental transplantation and autoimmunity, and important implications for the immune system development.Frontiers in Bioscience 02/2007; 12:3302-11. · 3.52 Impact Factor
Article: Tolerogenic effect of non-inherited maternal antigens in hematopoietic stem cell transplantation.[show abstract] [hide abstract]
ABSTRACT: 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.Frontiers in immunology. 01/2012; 3:135.