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

对病毒特异性CD8 T细胞的多方面分析揭示了妊娠期间针对巨细胞病毒感染状态的独特免疫特征

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作者: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

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 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.

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