The establishment of a cytomegalovirus -specific CD8+ T-cell threshold by kinetic modeling for the prediction of post-hemopoietic stem cell transplant reactivation

Jing Zhang; Jinpeng Cao; Runhui Zheng; Mengqiu Yu; Zhengfang Lin; Caixia Wang; James McCluskey; Ji Yang; Zhenjun Chen; Alexandra J Corbett; Pengxing Cao; Wenjian Mo; Zhongfang Wang

doi:10.1016/j.isci.2022.105340

The establishment of a cytomegalovirus -specific CD8⁺ T-cell threshold by kinetic modeling for the prediction of post-hemopoietic stem cell transplant reactivation

iScience. 2022 Oct 12;25(11):105340. doi: 10.1016/j.isci.2022.105340. eCollection 2022 Nov 18.

Authors

Jing Zhang^{1

2}, Jinpeng Cao^{1

2}, Runhui Zheng³, Mengqiu Yu¹, Zhengfang Lin¹, Caixia Wang⁴, James McCluskey⁵, Ji Yang¹, Zhenjun Chen⁵, Alexandra J Corbett⁵, Pengxing Cao⁶, Wenjian Mo⁴, Zhongfang Wang^{1

2}

Affiliations

¹ State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
² Guangzhou Laboratory, Bio-Island, Guangzhou, China.
³ Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
⁴ Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁵ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
⁶ School of Mathematics and Statistics, The University of Melbourne, Melbourne, VIC 3010, Australia.

Abstract

The dynamic interaction between the CMV virus and host immune response remains obscure, thus hindering the diagnosis and therapeutic management of patients with HSCT. The current diagnosis of CMV viremia depends on viral load estimation. Medical intervention based on viral load, can be unnecessary or poorly timed for many patients. Here we examined the clinical features and blood samples of patients with HSCT and assessed the CMV reactivation kinetics and corresponding CMV antigen-specific T-cell response in individual patients based on a peptide pool stimulation T-cell assay, which showed that CMV-specific CD8⁺ T cells were more suitable to be a diagnosis indicator for suppressing CMV reactivation. Using ROC analysis, we defined and verified a CMV-specific CD8⁺ T-cell counts threshold (925 cells/10⁶ PBMCs) as an indicator of CMV reactivation post-HSCT, and suggested that use of this threshold would provide more accurate guidance for prompt medication and better management of CMV infection post-HSCT.

Keywords: Health sciences; Immune system; Immunology; Mathematical biosciences; Stem cells research; Virology.

Grants and funding

R01 AI148407/AI/NIAID NIH HHS/United States