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Committed Th1 CD4+ T cell differentiation blocks pregnancy induced Foxp3 expression with antigen specific fetal loss
- Publication Year :
- 2014
-
Abstract
- Pregnancy stimulates induced Foxp3 expression among maternal CD4+ T cells with fetal specificity. Although sustained maternal regulatory CD4+ T cell (Treg) expansion is essential for maintaining fetal tolerance during pregnancy, the necessity for Foxp3+ cells with fetal specificity remains undefined. In this study, we demonstrate that mitigating Treg differentiation among maternal CD4+ T cells with a single surrogate fetal specificity elicits Ag-specific fetal loss. Using recombinant Listeria monocytogenes to prime stably differentiated Th1 CD4+ T cells with fetal I-Ab:2W1S55–68 specificity refractory to pregnancy-induced Foxp3 expression, we show that Ag delivery by cytoplasmic L. monocytogenes causes selective loss of 2W1S+ offspring through CD4 cell– and IFN-γ–dependent pathways. In contrast, CD4+ T cells primed by L. monocytogenes restricted from the cell cytoplasm are markedly more plastic for induced Foxp3 expression, with normal pregnancy outcomes. Thus, committed Th1 polarization blocks pregnancy induced Treg differentiation among maternal CD4+ T cells with fetal specificity and triggers Ag-specific fetal loss.
- Subjects :
- CD4-Positive T-Lymphocytes
Adoptive cell transfer
T cell
Cellular differentiation
Immunology
Biology
T-Lymphocytes, Regulatory
Article
Andrology
Interferon-gamma
Mice
Mice, Congenic
Fetus
Antigen
Pregnancy
medicine
Immunology and Allergy
Animals
Interferon gamma
Listeriosis
Antigens
Mice, Inbred BALB C
FOXP3
Cell Differentiation
Forkhead Transcription Factors
Th1 Cells
medicine.disease
Flow Cytometry
Adoptive Transfer
Listeria monocytogenes
Mice, Inbred C57BL
medicine.anatomical_structure
Host-Pathogen Interactions
Female
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....51f11735717e2124fbaa363f268fddec