Maternal T Cells in the Human Placental Villi Support an Allograft Response during Noninfectious Villitis
| Autor: | Elizabeth Ann L. Enninga, Clive M. Gray, Patrick Raber, Sarah E. Kerr, Erica L Johnson, Rana Chakraborty, Reade A. Quinton, Rodrigo Ruano, Nadia M Ikumi |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Graft Rejection Placenta Diseases T-Lymphocytes T cell Immunology Epitopes T-Lymphocyte Article Epitope Cohort Studies Young Adult 03 medical and health sciences Fetus 0302 clinical medicine Antigen Cell Movement HLA Antigens Pregnancy Placenta medicine Humans Immunology and Allergy Antigens Viral Inflammation business.industry Allografts medicine.disease medicine.anatomical_structure Genes T-Cell Receptor beta Female Chorionic Villi business Villitis of unknown etiology CD8 030215 immunology |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | During human pregnancy, proinflammatory responses in the placenta can cause severe fetal complications, including growth restriction, preterm birth, and stillbirth. Villitis of unknown etiology (VUE), an inflammatory condition characterized by the infiltration of maternal CD8+ T cells into the placenta, is hypothesized to be secondary to either a tissue rejection response to the haploidentical fetus or from an undiagnosed infection. In this study, we characterized the global TCR β-chain profile in human T cells isolated from placentae diagnosed with VUE compared with control and infectious villitis–placentae by immunoSEQ. Immunosequencing demonstrated that VUE is driven predominantly by maternal T cell infiltration, which is significantly different from controls and infectious cases; however, these T cell clones show very little overlap between subjects. Mapping TCR clones to common viral epitopes (CMV, EBV, and influenza A) demonstrated that Ag specificity in VUE was equal to controls and significantly lower than CMV-specific clones in infectious villitis. Our data indicate VUE represents an allograft response, not an undetected infection. These observations support the development of screening methods to predict those at risk for VUE and the use of specific immunomodulatory therapies during gestation to improve outcomes in affected fetuses. |
| Databáze: | OpenAIRE |
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