Dataset Information

Maternal CD4? and CD8? T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice.

ABSTRACT: Tolerance of the maternal immune system in pregnancy is important for successful pregnancy because the semiallogeneic fetus may be subject to antifetal responses. We examined maternal tolerance to the fetus using a murine system in which a model paternally inherited antigen, ovalbumin (OVA), is expressed exclusively in the fetus and placenta. By employing T cell receptor (TCR) transgenic mice specific for major histocompatibility complex class I- or class II-restricted epitopes of OVA (OT-I and OT-II) as mothers, we investigated the fate of fetus-specific CD8? and CD4? T cells, respectively, during gestation. Both OVA-specific CD8? and CD4? T cells displayed an activated phenotype in the peripheral lymphoid tissues of OVA-bred OT-I and OT-II mice, consistent with their encounter of fetal antigen. Whereas a small percentage of OVA-specific CD4? T cells were deleted in the periphery and thymus of OVA-bred OT-II mice, with evidence of TCR downregulation in the remaining T cells, deletion and TCR downregulation were not observed in OVA-bred OT-I mice. Both CD4? and CD8? T cells upregulated inducible costimulator expression in response to the fetal antigen, but only CD4? T cells consistently upregulated the inhibitory receptors programmed cell death 1 and cytotoxic T lymphocyte antigen-4. More regulatory T cells (Tregs) were present in pregnant OVA-bred than in WT-bred OT-II mice, revealing that Tregs expanded specifically in response to the fetal antigen. These data indicate that several mechanisms tolerize fetal antigen-specific maternal CD4? T cells, whereas tolerance of fetal antigen-specific CD8? T cells is less effective. The importance of these mechanisms is underscored by the finding that fetal loss occurs in OVA-bred OT-I but not OT-II mice.

SUBMITTER: Perchellet AL

PROVIDER: S-EPMC4076394 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal CD4⁺ and CD8⁺ T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice.

Perchellet Antoine L AL Jasti Susmita S Petroff Margaret G MG

Biology of reproduction 20131031 4

Tolerance of the maternal immune system in pregnancy is important for successful pregnancy because the semiallogeneic fetus may be subject to antifetal responses. We examined maternal tolerance to the fetus using a murine system in which a model paternally inherited antigen, ovalbumin (OVA), is expressed exclusively in the fetus and placenta. By employing T cell receptor (TCR) transgenic mice specific for major histocompatibility complex class I- or class II-restricted epitopes of OVA (OT-I and ...[more]

PMID: 24025737

Similar Datasets

Project description:Minor Histocompatibility (H) antigens are major histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)-bound peptides that differ between allogeneic hematopoietic stem cell transplantation (HCT) recipients and their donors as a result of genetic polymorphisms. Some minor H antigens can be used as therapeutic T cell targets to augment the graft-vs.-leukemia (GVL) effect in order to prevent or manage leukemia relapse after HCT. Graft engineering and post-HCT immunotherapies are being developed to optimize delivery of T cells specific for selected minor H antigens. These strategies have the potential to reduce relapse risk and thereby permit implementation of HCT approaches that are associated with less toxicity and fewer late effects, which is particularly important in the growing and developing pediatric patient. Most minor H antigens are expressed ubiquitously, including on epithelial tissues, and can be recognized by donor T cells following HCT, leading to graft-vs.-host disease (GVHD) as well as GVL. However, those minor H antigens that are expressed predominantly on hematopoietic cells can be targeted for selective GVL. Once full donor hematopoietic chimerism is achieved after HCT, hematopoietic-restricted minor H antigens are present only on residual recipient malignant hematopoietic cells, and these minor H antigens serve as tumor-specific antigens for donor T cells. Minor H antigen-specific T cells that are delivered as part of the donor hematopoietic stem cell graft at the time of HCT contribute to relapse prevention. However, in some cases the minor H antigen-specific T cells delivered with the graft may be quantitatively insufficient or become functionally impaired over time, leading to leukemia relapse. Following HCT, adoptive T cell immunotherapy can be used to treat or prevent relapse by delivering large numbers of donor T cells targeting hematopoietic-restricted minor H antigens. In this review, we discuss minor H antigens as T cell targets for augmenting the GVL effect in engineered HCT grafts and for post-HCT immunotherapy. We will highlight the importance of these developments for pediatric HCT.

Dataset Information

Maternal CD4? and CD8? T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice.

Publications

Maternal CD4⁺ and CD8⁺ T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets