Maternal CD8+ T-cell depletion alleviates intrauterine inflammation-induced perinatal brain injury

Jun Lei, Li Xie, Hongxi Zhao, Candice Gard, Julia L. Clemens, Michael W. Mclane, Mia C. Feller, Maide Ozen, Christopher Novak, Wael Alshehri, Nader Alhejaily, Yahya Shabi, Jason M. Rosenzweig, Andrea Facciabene, Irina Burd

Research output: Contribution to journalArticle

Abstract

We investigated the mechanisms by which CD8+ T-cell trafficking in placenta contributes to perinatal brain injury by studying effects of maternal CD8+ T-cell depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal CD8+ T cells were depleted with anti-CD8+ antibodies. IUI was induced with lipopolysaccharide (LPS). DEP was confirmed using flow cytometry. Preterm birth rate was evaluated. Offspring neurologic sequelae were assessed by Nissl staining, immune arrays, confirmatory individual TaqMan® gene assays, and neurobehavioral tests. DEP did not significantly prevent LPS-induced preterm birth but improved neurobehavioral performance (P < .001) and increased cortical neuronal density (P < .05) in LPS-exposed pups compared to controls. These changes were associated with decreased CCL3 and CXCL10 and increased CCL5 in DEP LPS-exposed mice. We demonstrate that DEP reduces perinatal brain injury following IUI. This supports a role for maternal CD8+ T-cell trafficking in placenta in mediating perinatal brain injury separate from preterm birth mechanisms.

Original languageEnglish (US)
JournalAmerican Journal of Reproductive Immunology
DOIs
Publication statusAccepted/In press - Jan 1 2017

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Keywords

  • Lipopolysaccharide
  • Lymphocyte trafficking
  • Neurobehavior
  • Placenta
  • Preterm birth

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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