Metabolic and Functional Study of γδ T Cells in Critically Ill Patients

NCT07680816 | Not Yet Recruiting

• 1 other identifier: zjc202612
• Study Type: observational
• Target: 105
• Locations: 0 countries
• Sites: N/A

Brief Summary

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδT cells in critically ill patients with and without sepsis. Emerging evidence indicates that γδT cells, as a bridge between innate and adaptive immunity, play a critical role in early anti-infection defense during sepsis. However, the functional status and underlying regulatory mechanisms of cytotoxic γδT cells in septic patients remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed that cytotoxic γδT cells from septic patients exhibit significant alterations in cytotoxicity-associated molecules (GZMB, PRF1, GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes, particularly COX6C, which correlates with cytotoxic effector molecule expression. This study aims to systematically characterize the proportion, cytotoxicity, and mitochondrial metabolic function of circulating cytotoxic γδT cells across three cohorts: healthy controls, critically ill non-septic patients, and critically ill septic patients. By integrating flow cytometry, mitochondrial function assays, and functional validation experiments, we seek to elucidate the role of COX6C-mediated mitochondrial metabolic abnormalities in cytotoxic γδT cell dysfunction, providing theoretical basis for understanding immune dysregulation in sepsis and identifying novel therapeutic targets.

Conditions

Sepsis; Critical Illness; Immunosuppression; MODS; Mitochondrial Diseases; Dysbiosis; γδ T Cells

Outcome Measures

Primary Outcomes (1)

• Change in the Proportion of Cytotoxic γδT Cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) Among Total γδT Cells

  Flow cytometric quantification of the frequency of Cytotoxic γδT cells, defined as TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺ cells, as a percentage of total γδT cells (TCRγδ⁺) in peripheral blood. This subset represents the cytotoxic effector population critical for early anti-infection defense.

  Day 2 post-ICU admission

Secondary Outcomes (22)

• Change in COX6C Expression in Cytotoxic γδT Cells

  Day 2 post-ICU admission

• Change in Cytotoxic Molecule Expression in Cytotoxic γδT Cells

  Day 2 post-ICU admission

• Change in Mitochondrial Mass in Cytotoxic γδT Cell

  Day 2 post-ICU admission

• Change in Mitochondrial Membrane Potential (TMRE) in Cytotoxic γδT Cells

  Day 2 post-ICU admission

• Change in Mitochondrial Membrane Potential (JC-1) in Cytotoxic γδT Cells

  Day 2 post-ICU admission

Study Arms (3)

Healthy Controls (NHCs)

Healthy volunteers without acute or chronic major diseases, aged ≥18 years, who have provided written informed consent. Participants undergo a single blood draw and rectal swab collection.

Critically Ill Non-Septic Patients (CI-NS)

Patients admitted to the ICU meeting the criteria for critical illness but without sepsis, as determined by the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points excluded). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.

Critically Ill Septic Patients (CI-Sep)

Patients admitted to the ICU meeting the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises three distinct groups: healthy volunteers, non-septic critically ill patients, and septic critically ill patients admitted to the intensive care unit. Sepsis is defined according to the Sepsis-3 criteria (infection with an acute increase in SOFA score ≥2 points), while critical illness is based on standard ICU admission criteria. All participants must be aged ≥18 years and provide written informed consent (from the participant or a legally authorized representative for those unable to consent). Key exclusion criteria include known immunodeficiency, recent use of T-cell-targeted immunosuppressants or immune checkpoint inhibitors, expected ICU stay \<24 hours, pregnancy, active major bleeding, or inability to obtain consent. Consecutive enrollment will take place at the Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, with follow-up through 90 days after enrollment.

You may qualify if:

• Healthy Control Group (NHC):
• Age ≥ 18 years.
• No acute or chronic major diseases.
• Provide written informed consent.
• Non-septic Critical Illness Group (CI-NS):
• Age ≥ 18 years.
• Admitted to the ICU and meeting the definition of critical illness.
• Excluded from sepsis according to the Sepsis-3 criteria (infection + ΔSOFA ≥ 2 points).
• Written informed consent provided by the participant or legally authorized representative.
• Septic Critical Illness Group (CI-Sep):
• Age ≥ 18 years.
• Admitted to the ICU and meeting the Sepsis-3 criteria (infection + ΔSOFA ≥ 2 points).
• Written informed consent provided by the participant or legally authorized representative.

You may not qualify if:

• Age \< 18 years.
• Known immunodeficiency, HIV infection, active hematologic malignancy, or history of hematopoietic stem cell or solid organ transplantation within the past 3 months.
• Receipt of T-cell-targeted immunosuppressive therapy (e.g., antithymocyte globulin, calcineurin inhibitors, mycophenolate mofetil, methotrexate, or high-dose corticosteroids \>1 mg/kg/day prednisone equivalent) before ICU admission or within 24 hours after ICU admission.
• Use of immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1/CTLA-4 antibodies) within the past 6 weeks.
• Expected ICU stay \< 24 hours or imminent risk of death (moribund state).
• Pregnancy or breastfeeding.
• Active major bleeding.
• Inability to obtain informed consent.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Sepsis; Critical Illness; Multiple Organ Failure; Mitochondrial Diseases; Dysbiosis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Shock; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 2, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-07