Multifaceted profiling of virus-specific CD8 T cells reveals distinct immune signatures against cytomegalovirus infection states during pregnancy.

Journal: iScience
Published Date: Apr 11, 2025

Abstract

Anti-cytomegalovirus (CMV) serological testing, including the IgG avidity index (AI), is used to assess CMV infection phases during pregnancy. However, little is known about anti-CMV cellular immunity during pregnancy, particularly its relation to serological diagnosis. Herein, using MHC-dextramer single-cell RNA sequencing and flow cytometry, we characterized IE1 and pp65 CMV-antigen specific CD8 T cells from pregnant women with different anti-CMV serological patterns, including IgGIgM/AI-low, IgGIgM/AI-high, and IgGIgM. In IgGIgM/AI-low and IgGIgM/AI-high specimens, CMV-specific T cells consisted largely of effectors, with a minor but characteristic proportion of memory T cells, including HLA-DR-positive memory precursors and granzyme K-high memory cells reactive to IE1. Conversely, IgGIgM cases had a distinctive expansion of pp65-specific terminally differentiated T effector memory with a signature of convergent clonal selection. Our findings revealed that different CMV infection phases have characteristic patterns of CD8 cell phenotype and antigen recognition, potentially offering a new approach for assessing congenital infection risk.

Authors

  • Ayumi Taguchi
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Fumi Misumi
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • Shunsuke Teraguchi
    Faculty of Data Science, Shiga University, Shiga 522-8522, Japan.
  • Takeshi Nagamatsu
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • Shuhei Sakakibara
    Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.
  • Tomohiro Otani
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • Mari Ichinose
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • David Priest
    Laboratory of Human Single Cell Immunology, WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.
  • Kazuki Nakajima
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • Junko Nakamura
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • Ryoko Sawada
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • Tatsuo Suzutani
    Department of Microbiology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Toshiyuki Ikeda
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • Yutaka Nagura
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • Takayuki Iriyama
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • Daisuke Okuzaki
    Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.
  • Hitoshi Okazaki
    Department of Transfusion Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • James B Wing
    Laboratory of Human Single Cell Immunology, WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan.
  • Yasushi Hirota
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
  • Yutaka Osuga
    Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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