Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis.

Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice.

This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Inflammatory Response

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Jiancheng Zhang, Dr.
      • Contact: Jiancheng Zhang, Dr.; Phone Number: +8613554105815; Email: zhjcheng1@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

patients with sepsis defined based on Sepsis 3.0 criteria

Description

Inclusion Criteria:

Patients aged 18-60 years old without restriction of gender, race, religion, creed or nationality; No sedative drugs with elimination half-life were used before inclusion in the study; Patients and/or their family members know and agree to participate in the trial.

Exclusion Criteria:

History of solid organ or bone marrow transplantation; Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma; Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc); Pregnancy or lactation; Chronic nephrosis; Severe chronic liver disease (child-Pugh: Grade C); alcohol or opioid dependence, mental illness, or severe cognitive impairment; Patients and/or their family members refuse to participate in the trial.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
septic patients; patients with sepsis defined based on Sepsis 3.0 criteria within 24 hours after admission
healthy control group; healthy adults

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute number of CD8+T subsets in the peripheral blood (0 hour)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	0 hour after study inclusion
Absolute number of CD8+T subsets in the peripheral blood (24 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	24 hours after study inclusion
Absolute number of CD8+T subsets in the peripheral blood (48 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	48 hours after study inclusion
Absolute number of CD8+T subsets in the peripheral blood (72 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	72 hours after study inclusion
proliferation of CD8+T subsets in the peripheral blood (0 hour)	expression of Ki67 in Tcm and Tem	0 hour after study inclusion
proliferation of CD8+T subsets in the peripheral blood (24 hours)	expression of Ki67 in Tcm and Tem	24 hours after study inclusion
proliferation of CD8+T subsets in the peripheral blood (48 hours)	expression of Ki67 in Tcm and Tem	48 hours after study inclusion
proliferation of CD8+T subsets in the peripheral blood (72 hours)	expression of Ki67 in Tcm and Tem	72 hours after study inclusion
ICU length of stay	Length of stay in the ICU	up to 4 weeks
PD-1 expression of CD8+T subsets in the peripheral blood (24 hours)	expression of PD-1 in Tcm and Tem	24 hours after study inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute physiology and chronic health evaluation (APACHE) Ⅱ score	0-67, higher scores correspond to more severe disease and a higher risk of death	24 hours after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score	0-67, higher scores correspond to more severe disease and a higher risk of death	48 hours after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score	0-67, higher scores correspond to more severe disease and a higher risk of death	72 hours after study inclusion
Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	0 hour after study inclusion
Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	24 hours after study inclusion
Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	48 hours after study inclusion
Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	72 hours after study inclusion
Mechanical ventilation time after inclusion	Patients requiring mechanical ventilation after study inclusion	up to 4 weeks
Total hospital length of stay	Total length of hospital stay	up to 4 weeks
In-hospital mortality	Mortality rates for the entire period of hospitalization	up to 4 weeks
90-day readmission rate	Percentage of readmission to hospital within 90 days of study inclusion	up to 4 weeks
Infection complications	Pulmonary infection, urinary tract infection, bloodstream infections, etc	up to 4 weeks
Acute physiology and chronic health evaluation (APACHE) Ⅱ score	0-67, higher scores correspond to more severe disease and a higher risk of death	0h after study inclusion
Plasma cytokine levels	IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α	0 hour after study inclusion
Plasma cytokine levels	IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α	24 hours after study inclusion
Plasma cytokine levels	IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α	48 hours after study inclusion
Plasma cytokine levels	IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α	72 hours after study inclusion
Peripheral blood PMN-MDSC levels	Frequencies and absolute numbers of total PMN-MDSCs (CD45⁺ CD11b⁺ CD15⁺ CD14- CD33⁺ HLA-DRˡᵒʷ) and the CXCR2⁺ PD-L1⁺ PMN-MDSC subpopulation, assessed via flow cytometry.	Within 72 hours of sepsis diagnosis or ICU admission.

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: sepsis; inflammatory response; CD8+ T cell; central memory CD8+ T cell
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis
• Other Study ID Numbers: ZJC202304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No