Characterisation of CTL directed towards non-inherited maternal alloantigens in human cord blood

Moretta, Antonia; Locatelli, Franco; Mingrat, G.; Rondini, G; Montagna, Daniela; Comoli, Patrizia; Gandossini, S; Montini, Enrica; Labirio, Massimo; Maccario, Rita

doi:10.1038/sj.bmt.1702054

Cited by 36 publications

(39 citation statements)

References 21 publications

(34 reference statements)

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“…Frequencies of CTL precursor (CTLp), Th lymphocyte precursor (HTLp), and MLR were reported as methods to detect an individual reactivity to NIMA in vitro to date (44)(45)(46). Besides the analysis of CTLp and HTLp frequencies and MLR, which are also contradictory, an established test system has not been available for the prediction of outcome after HSCT.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

Araki

Hirayama

Azuma

et al. 2010

The Journal of Immunology

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The immunologic effects of developmental exposure to noninherited maternal Ags (NIMAs) are quite variable. Both tolerizing influence and inducing alloreaction have been observed on clinical transplantation. The role of minor histocompatibility Ags (MiHAs) in NIMA effects is unknown. MiHA is either matched or mismatched in NIMA-mismatched transplantation because a donor of the transplantation is usually limited to a family member. To exclude the participation of MiHA in a NIMA effect for MHC (H-2) is clinically relevant because mismatched MiHA may induce severe alloreaction. The aim of this study is to understand the mechanism of NIMA effects in MHC-mismatched, MiHA-matched hematopoietic stem cell transplantation. Although all offsprings are exposed to the maternal Ags, the NIMA effect for the H-2 Ag was not evident. However, they exhibit two distinct reactivities, low and high responder, to NIMA in utero and during nursing depending on the degree of maternal microchimerism. Low responders survived longer with less graft-versus-host disease. These reactivities were correlated with Foxp3 expression of peripheral blood CD4+CD25+ cells after graft-versus-host disease induction and the number of IFN-γ–producing cells stimulated with NIMA pretransplantation. These observations are clinically relevant and suggest that it is possible to predict the immunological tolerance to NIMA.

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Section: Discussionmentioning

confidence: 99%

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

Araki

Hirayama

Azuma

et al. 2010

The Journal of Immunology

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“…13,18 Although there have been a number of conflicting debates on this 'maternal-fetal effect', originally reported as specific B cell unresponsiveness to non-inherited maternal HLA antigens in heavily transfused adult patients, 7 recent clinical observations have begun to substantiate the post-partum persistence of such bidirectional tolerance which appears to have important implications in human transplantation medicine. Umbilical cord blood mononuclear cells have been demonstrated to produce different phenotypes of cytotoxic lymphocytes when exposed to maternal or paternal cells, 19 and reported to show weaker alloreactive responses to maternal blood cells than to paternal cells. 20 Peripheral blood lymphocytes from mother and infant still exhibited markedly depressed responses to one another even at 6 months following delivery.…”

Section: Discussionmentioning

confidence: 99%

Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts

Tamaki

Ichinohe

Matsuo

et al. 2001

Bone Marrow Transplant

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Summary:During the reproductive period, mothers and offspring exchange hematopoietic cells and develop a form of immunological tolerance bidirectionally. To examine whether previous experience of such communication has any remote effect when maternal hematopoietic cells are later transplanted to the children, we retrospectively compared the outcomes of blood and marrow stem cell transplantation from maternal donors (n = 46) to those from paternal donors (n = 50) by using the database of the Japanese nationwide surveys for adult hematopoietic cell transplants between 1990 and 1998. At 5 years, recipients of maternal hematopoietic cells had a significantly higher overall survival than patients receiving paternal grafts (60% vs 32%, P = 0.006). Although no significant difference was observed in the occurrence of severe acute GVHD (grade уIII) and the relapse of malignant diseases between two groups, the probability of non-relapse treatment-related mortality was significantly lower after maternal donor transplants. Furthermore, multivariate analysis revealed that parental donor type was the only factor significantly associated with overall survival. In conclusion, our analysis indicates superior survival of maternally donated recipients in hematopoietic stem-cell transplantations from biological parents. This finding has important implications in the selection of alternative familial donors, and warrants further prospective analysis of parental donor transplantations. Allogeneic hematopoietic stem cell transplantation after myeloablative or nonmyeloablative chemoradiotherapy is a potentially curative treatment for various hematologic and hereditary diseases. 1,2 Since the availability of an HLAidentical sibling donor is often limited, most patients eligible for allogeneic stem cell transplants have to seek an alternative donor who is not fully histocompatible with themselves. 3-5 HLA-phenotypically matched or partiallymismatched parents represent an important stem-cell source for such patients, because both mother and father genetically share at least one HLA haplotype with their children.Maternal and paternal donations differ in the transplant situation because only the mother-child pair has had the opportunity to establish bidirectional immunological tolerance during pregnancy and maybe thereafter. For example, maternal peripheral blood lymphocytes were shown to be immunologically unresponsive to those of the infant for several months following delivery. 6 On the other hand, about half of the patients receiving multiple transfusions as adults did not form antibodies against the non-inherited maternal HLA antigens, 7 indicating the persistence of acquired B cell unresponsiveness to maternal antigens into adult life. More surprisingly, semi-allogeneic fetal hematopoietic cells were detectable from parous women not only during gestation but also many years after childbirth, [8][9][10][11] suggesting a long-lasting form of the maternal tolerance to fetal HLA antigens of paternal origin.To date, the role of such previo...

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“…39 Selection of untreated donor CB for transplantation: noninherited maternal allele matching One area that needs further exploration and unique to CB is the potential exploitation of noninherited maternal (NIMA) and paternal (NIPA) alleles. 43 A fetus is a haplotype match with the mother. In utero, the fetal lymphocytes, which are immunocompetent from 18 weeks gestation, are kept in a state of nonresponsiveness to the mismatching maternal antigens.…”

Section: Selection Of Unrelated Donor Cb For Transplantation: Cell Dosementioning

confidence: 99%

Selection of cord blood unit(s) for transplantation

Wall

Chan

2008

Bone Marrow Transplant

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Selection of cord blood (CB) units for transplantation involves combining both cell dose and HLA matching as independent yet overlapping variables. Cell dose and cell yield at the time of transplant are critical given that the transplants are being performed with minimal cells for reliable engraftment. In transplants for malignant disorders, the greater allogenicity and lower relapse rate associated with the less well-matched units balance any benefit of better HLA matching on TRM. The only factor that has repeatedly been associated with improved outcome post CB transplant is cell dose. The CB inventories are rapidly increasing in size and the quality of CB units being banked (larger, better characterized) is improving. With this, some of our current limitations in CB availability will soon become moot. Explorations into CB expansion and multiple CB unit transplants are addressing the limited cell doses attainable with a single CB collection. [1][2][3][4] At this point, one must conclude that bigger is better when selecting CB units for transplantation.

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Characterisation of CTL directed towards non-inherited maternal alloantigens in human cord blood

Cited by 36 publications

References 21 publications

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts

Selection of cord blood unit(s) for transplantation

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