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Immune cell cross-talk occurs mainly in lymphoid organs. However, systemic cell interaction specific to coronavirus disease 2019 has not been well characterized. Here, by employing single-cell RNA sequencing and imaging flow cytometry analysis, we unraveled, in peripheral blood, a heterogeneous group of cell complexes formed by the adherence of CD14+ monocytes to different cytotoxic lymphocytes, including SARS-CoV-2\u2013specific CD8+ T cells, \u03b3\u03b4 T cells, and natural killer T cells. These lymphocytes attached to CD14+ monocytes that showed enhanced inflammasome activation and pyroptosis-induced cell death in progression stage; in contrast, in the convalescent phase, CD14+ monocytes with elevated antigen presentation potential were targeted by cytotoxic lymphocytes, thereby restricting the excessive immune activation. Collectively, our study reports previously unrecognized cell\u2013cell interplay in the SARS-CoV-2\u2013specific immune response, providing new insight into the intricacy of dynamic immune cell interaction representing antiviral defense.<\/jats:p>","DOI":"10.1093\/infdis\/jiae048","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:11:19Z","timestamp":1706515879000},"page":"5-14","source":"Crossref","is-referenced-by-count":6,"title":["Cytotoxic Lymphocyte-Monocyte Complex Reflects the Dynamics of Coronavirus Disease 2019 Systemic Immune Response"],"prefix":"10.1093","volume":"230","author":[{"given":"Jiajia","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine"},{"name":"Shanghai Immune Therapy Institute, Renji Hospital and Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University School of 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