Pregnancy Alters the Proliferation and Apoptosis of Mouse Splenic Erythroid Lineage Cells and Leukocytes1

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.

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“…1A). These observations are consistent with previous studies on the effects of pregnancy on lymphoid tissues [29,30].…”

Section: Fetus-specific Cd4 þ T Cells Are Activated and Deleted In Lysupporting

confidence: 94%

Maternal CD4+ and CD8+ T Cell Tolerance Towards a Fetal Minor Histocompatibility Antigen in T Cell Receptor Transgenic Mice1

Perchellet

Jasti

Petroff

2013

Biology of Reproduction

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“…This may have either changed their phenotype or selected a specialized subset of CD8 T cells not normally present in pregnant B6 mice. However, we have shown that pregnancy in normal mice supports turnover in the CD8 T-cell population, 21,22 and it is likely that such homeostatic turnover occurs similarly, but perhaps to a slightly greater extent in CD8 T cells transferred to Rag1 À/À mice and in CD8 T cells from normal B6 mice under the influence of pregnancy and PP.…”

Section: Discussionmentioning

confidence: 80%

“…[21][22][23][24] We have studied T-cell homeostasis in mice and observed changes in the maternal immune system that persist PP. [21][22][23][25][26][27] There may be accumulation of TREGs in PP that may protect subsequent pregnancies.…”

Section: Introductionmentioning

confidence: 99%

Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice

et al. 2017

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Pregnancy manifests changes in the vascular and immune systems that persist postpartum (PP), have important implications for future pregnancies, and may modify responses to cardiovascular stress in late life. The association between immune and vascular function and the generation or progression of cardiovascular disease beg the question of whether altered immunity modifies pregnancy-induced changes in the vasculature. Our objective was to compare changes in the function and remodeling of systemic resistance vessels 4 weeks PP in normal C57BL/6 (B6), and immunodeficient mice recombinase 1-deficient/B6 (Rag1). Immune deficiency did not change the responsiveness to acetylcholine (ACh) and phenylephrine at baseline but decreased arterial distensibility and increased stiffness PP. Adoptive transfer of CD8 T cells into Rag1 À/À mice decreased the response to ACh while increasing distensibility and wall thickness. When compared to PP Rag1 À/À , vessels from PP CD4-deficient mice, which have B cells and CD8 T cells, but no CD4 cells, show increased distensibility and decreased responsiveness to ACh in a pattern similar to that seen in Rag1 À/À given CD8 T cells prior to mating. These studies suggest a key role for T cell, particularly CD8 T cell, associated factors in the PP remodeling of maternal resistance vessels.

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“…Such cells undergo expansion in mid-gestation and persist throughout pregnancy in mice [18]. Nucleated erythroid cells are maintained in the circulation throughout the neonatal period and diminish as age progresses in humans [20] and in mice [19, 21].…”

Section: Introductionmentioning

confidence: 99%

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

Miller

Romero

Unkel

et al. 2018

Journal of Leukocyte Biology

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Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of pro-inflammatory cytokines and a reduction in the release of TGFβ. Moreover, PTL-derived neonatal CD71+ erythroid cells: 1) modestly altered CD8+ T cell activation; 2) inhibited conventional CD4+ and CD8+ T-cell expansion; 3) suppressed the expansion of CD8+ regulatory T cells,; 4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and 5) indirectly modulated T-cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal T-cell and myeloid responses and their direct contact with maternal mononuclear cells induces a pro-inflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor.

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Pregnancy Alters the Proliferation and Apoptosis of Mouse Splenic Erythroid Lineage Cells and Leukocytes1

Cited by 32 publications

References 30 publications

Maternal CD4+ and CD8+ T Cell Tolerance Towards a Fetal Minor Histocompatibility Antigen in T Cell Receptor Transgenic Mice1

Maternal CD4+ and CD8+ T Cell Tolerance Towards a Fetal Minor Histocompatibility Antigen in T Cell Receptor Transgenic Mice1

Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

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