Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens

Opiela, Shannon J.; Levy, Robert B.; Adkins, Becky

doi:10.1182/blood-2007-08-106500

Cited by 25 publications

(25 citation statements)

References 63 publications

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“…The relationship between tolerogenic effect and MMc are consistent with a report of Dutta et al They described the correlation between MMc and NIMA-specific Treg capable of suppressing both delayed type hypersensitivity and lymphoproliferative responses of effector T cells in a conventional NIMA mouse model (van Rood and Claas 1990;Andrassy, Kusaka et al 2003). Opiela et al described that transient exposure to low levels of NIMA alloantigens in early life may lead to long-term priming for both cytotoxic and helper T cell functions (Opiela, Levy et al 2008). …”

Section: Reactivity To Mismatched Histocompatibility Antgens; Tolerogsupporting

confidence: 83%

Major and Minor Histocompatibility Antigens to Non-Inherited Maternal Antigens (NIMA)

Hirayama¹,

Azuma²,

Komada³

2012

Histocompatibility

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Section: Reactivity To Mismatched Histocompatibility Antgens; Tolerogsupporting

confidence: 83%

Major and Minor Histocompatibility Antigens to Non-Inherited Maternal Antigens (NIMA)

Hirayama¹,

Azuma²,

Komada³

2012

Histocompatibility

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“…They described the correlation between MMc and NIMA-specific regulatory T cells capable of suppressing both delayed-type hypersensitivity and lymphoproliferative responses of effector T cells in conventional NIMA mouse model. Opiela et al (33) described that transient exposure to low levels of NIMA alloantigens in early life may lead to long-term priming for both cytotoxic and Th cell functions. In contrast, Aoyama et al (7) showed that both oral and in utero exposures to NIMA are required for the maximum induction of tolerance.…”

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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“…Indeed, noninherited maternal Ags (NIMAs) can be transferred to the fetus across the placenta or to the neonate via breast milk. Several studies demonstrated that, depending on the nature and the level of NIMAlike alloantigens present in newborns, tolerance or priming responses may take place, leading to long-term heart allograft survival (43) and suppression of graft-versus-host reaction (44) or to the opposite: acute rejection of renal grafts (45) and vigorous T cell responses (46). A recent study demonstrated that the human fetal immune system exposed to maternal microchimerism is able to mount NIMA alloantigen-specific CD4 + and CD8 + T cell responses and that CD4 + CD25 + Foxp3 + T cells able to control the fetal alloreactive T cells were induced by maternal alloantigens (47).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

Dubois

Deruytter

Adams

et al. 2010

The Journal of Immunology

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Th2-biased immune responses characterizing neonates may influence the later onset of allergic disease. The contribution of regulatory T cell populations in the prevention of Th2-driven pathologies in early life is poorly documented. We investigated the potential of CD8+ T cells stimulated at birth with alloantigens to modulate the development of allergic airway inflammation. Newborn mice were immunized with semiallogeneic splenocytes or dendritic cells (DCs) and exposed at the adult stage to OVA aeroallergens. DC-immunized animals displayed a strong Th1 and Tc1/Tc2 alloantigen-specific response and were protected against the development of the allergic reaction with reduced airway hyperresponsiveness, mucus production, eosinophilia, allergen-specific IgE and IgG1, and reduction of lung IL-4, IL-5, IL-10, and IL-13 mRNA levels. By contrast, splenocyte-immunized mice displayed a Th2 and a weak Tc2 alloantigen-specific response and were more sensitive to the development of the allergen-specific inflammation compared with mice unexposed at birth to alloantigens. DC-immunized animals displayed an important increase in the percentage of IFN-γ–producing CD8+CD44high, CD8+CD62Lhigh, and CD8+CD25+ subsets. Adoptive transfers of CD8+ T cells from semiallogeneic DC-immunized animals to adult β2m-deficient animals prevented the development of allergic response, in particular IgE, IL-4, and IL-13 mRNA production in an IFN-γ–dependent manner, whereas transfers of CD8+ T cells from semiallogeneic splenocyte-immunized mice intensified the lung IL-4 and IL-10 mRNA level and the allergen-specific IgE. These findings demonstrated that neonatal induction of regulatory CD8+ T cells was able to modulate key parameters of later allergic sensitization in a bystander manner, without recognition of MHC class I molecules.

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Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens

Cited by 25 publications

References 63 publications

Major and Minor Histocompatibility Antigens to Non-Inherited Maternal Antigens (NIMA)

Major and Minor Histocompatibility Antigens to Non-Inherited Maternal Antigens (NIMA)

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

Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

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