Mucosal Immunity

Pregnancy is a state of immunological balance during which the mother and the developing fetus must tolerate each other while maintaining sufficient immunocompetence to ward off potential threats. The site of closest contact between the mother and fetus is the decidua, which represents the...

KEY POINTS Maternal T cells drive VUE responses; fetal immune cells drive infectious etiology. Clonal overlap between VUE subjects is minimal but common in placental infection. Contrary to placental infection, VUE T cells do not recognize common viral epitopes. Abstract 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. Footnotes This work was supported by the National Institutes of Health (HD065987 to E.A.L.E., HD097843 to E.L.J. and R.C., and AI131566 to R.C. and C.M.G.), the Mayo Clinic Division of Anatomic Pathology (to S.E.K.), and the Mayo Clinic Center for Women's Health (to E.A.L.E.). The sequences presented in this article are available through immuneACCESS (clients.adaptivebiotech.com/pub/enninga-2020-ji) under accession number EALE2020JI. Abbreviations used in this article: FFPE formalin fixed, paraffin embedded FISH fluorescence in situ hybridization J joining NP-40 Nonidet P-40 RT room temperature V variable VUE villitis of unknown etiology. Received October 28, 2019. Accepted March 26, 2020. Copyright © 2020 by The American Association of Immunologists, Inc.

Innate immunity is a primordial system that has a primary role in lung antimicrobial defenses. Recent advances in understanding the recognition systems by which cells of the innate immune system recognize and respond to microbial products have revolutionized ...

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The human gut is colonized by trillions of bacteria as well as other microorganisms, collectively referred to as the “gut microflora.” This microflora plays an important role in metabolism as well as immunity, and alterations in its normal composition and pattern of colonization can...

This Review outlines the pathophysiology of Kawasaki disease and discusses the progress gained from experimental mouse models and their potential therapeutic translation to human disease.

In a recent PLoSONE study, researchers found that maternal cytotoxic T cells transferred via breast milk to suckling pups home to Peyer’s patches in the pups, and are much more active than the newborns’ cytotoxic T cells.

Credit: Toshio Hirano and Masaaki Murakami. Immunity.April 22, 2020 Research into how the SARS-CoV-2 virus induces death is suggesting...

Mucosal-associated invariant T (MAIT) cells are depleted from blood in patients with
advanced liver disease and show features of immune dysfunction. Because circulating MAIT cells differ from organ-resident MAIT cells, we aimed to investigate the frequency, phenotype, and function of peritoneal...

Abstract Objectives The activation of immune responses in mucosal tissues is a key factor for the development and sustainment of several pathologies including infectious diseases and autoimmune dis...

A study sheds new light on the body’s initial response to dengue virus (DENV) infection, describing the molecular diversity and specificity of the antibody response and identifying a heretofore unappreciated role for DENV-reactive IgA antibodies.