Multifaceted profiling of virus-specific CD8 T cells reveals distinct immune signatures against cytomegalovirus infection states during pregnancy
Ayumi Taguchi,
Fumi Misumi,
Shunsuke Teraguchi,
Takeshi Nagamatsu,
Shuhei Sakakibara,
Tomohiro Otani,
Mari Ichinose,
David Priest,
Kazuki Nakajima,
Junko Nakamura,
Ryoko Sawada,
Tatsuo Suzutani,
Toshiyuki Ikeda,
Yutaka Nagura,
Takayuki Iriyama,
Daisuke Okuzaki,
Hitoshi Okazaki,
James B. Wing,
Yasushi Hirota,
Yutaka Osuga
Affiliations
Ayumi Taguchi
Laboratory of Human Single Cell Immunology, WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan; Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, 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; Department of Genome Informatics, Research Institute for Microbial Diseases, The University of Osaka, Osaka 565-0871, Japan
Takeshi Nagamatsu
Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan; Department of Obstetrics and Gynecology, International University of Health and Welfare, Narita 286-8686, Japan; Corresponding author
Shuhei Sakakibara
Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, The University of Osaka, Osaka 565-0871, Japan; Graduate School of Medical Safety Management, Jikei University of Health Care Sciences, Osaka 532-0003, Japan; Corresponding author
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; Laboratory Sciences, Department of Health Sciences, School of Health and Social Service, Saitama Prefectural University, Saitama 343-0036, 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; Human Single Cell Immunology Team, Center for Infectious Disease Education and Research, 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; Human Single Cell Immunology Team, Center for Infectious Disease Education and Research, 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 113-8654, Japan
Summary: 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 IgG+IgM+/AI-low, IgG+IgM+/AI-high, and IgG+IgM−. In IgG+IgM+/AI-low and IgG+IgM+/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, IgG+IgM− 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.
