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

16 de septiembre de 2026 actualizado por: Jiancheng Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Subset-specific Metabolic Adaptation and Functional Remodeling of Gamma Delta T (γδ T) Cells in Critically Ill ICU Patients: A Single-center, Prospective, Observational Cohort Study.

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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Tipo de estudio

De observación

Inscripción (Estimado)

105

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Porcelana
    • Outside of the US
      • Wuhan, Outside of the US, Porcelana, 430022
        • Reclutamiento
        • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contacto:
          • Jiancheng Zhang, Dr.
          • Número de teléfono: 13554105815
          • Correo electrónico: zhjcheng1@126.com

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

Sí

Método de muestreo

Muestra no probabilística

Población de estudio

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.

Descripción

Inclusion Criteria:

  1. Healthy Control Group (NHC):

    • Age ≥ 18 years.
    • No acute or chronic major diseases.
    • Provide written informed consent.

  2. 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.

  3. 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.

Exclusion Criteria:

  • 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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

Cohortes e Intervenciones

Grupo / Cohorte
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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in the Proportion of Cytotoxic γδT Cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) Among Total γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in COX6C Expression in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Measurement of COX6C (mitochondrial respiratory chain complex IV subunit) expression levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at the mRNA level (by single-cell RNA sequencing) and protein level (by flow cytometry).
Day 2 post-ICU admission
Change in Cytotoxic Molecule Expression in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Flow cytometric quantification of the mean fluorescence intensity (MFI) of cytotoxic effector molecules including Granzyme B (GZMB), Perforin (PRF1), and Granulysin (GNLY) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Mitochondrial Mass in Cytotoxic γδT Cell
Periodo de tiempo: Day 2 post-ICU admission
Flow cytometric quantification of mitochondrial mass using MitoTracker Green FM staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Mitochondrial Membrane Potential (TMRE) in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Flow cytometric quantification of mitochondrial membrane potential using tetramethylrhodamine ethyl ester (TMRE) staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Mitochondrial Membrane Potential (JC-1) in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Flow cytometric quantification of mitochondrial membrane potential using JC-1 dye (red/green fluorescence ratio) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Oxygen Consumption Rate (OCR) in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Measurement of basal oxygen consumption rate reflecting oxidative phosphorylation (OXPHOS) capacity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Extracellular Acidification Rate (ECAR) in Cytotoxic γδT Cells
Periodo de tiempo: Day 2 post-ICU admission
Measurement of basal extracellular acidification rate reflecting glycolytic metabolic activity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Day 2 post-ICU admission
Change in Glycolytic Capacity of Cytotoxic γδT Cells at Serial Time Points
Periodo de tiempo: Day 0, Day 2, and Day 7 post-ICU admission
Longitudinal flow cytometric puromycin-incorporation assay (SCENITH method) to measure glycolytic capacity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, to track the temporal evolution of metabolic flexibility and stress-adaptive glycolytic reprogramming during the course of critical illness.
Day 0, Day 2, and Day 7 post-ICU admission
Change in Mitochondrial ROS Levels in Cytotoxic γδT Cells at Serial Time Points
Periodo de tiempo: Day 0, Day 2, and Day 7 post-ICU admission
Longitudinal flow cytometric quantification of mitochondrial reactive oxygen species (mitochondrial ROS) levels using MitoSOX Green staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, reflecting oxidative stress dynamics.
Day 0, Day 2, and Day 7 post-ICU admission
Change in Cytotoxic γδT Cell Migratory Function
Periodo de tiempo: Day 2 post-ICU admission
Assessment of Cytotoxic γδT cell (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) chemotactic and migratory capacity using Transwell migration assay.
Day 2 post-ICU admission
Change in Total γδT Cell Proportion at Serial Time Points
Periodo de tiempo: Day 0, Day 2, and Day 7 post-ICU admission
Longitudinal flow cytometric quantification of the frequency of total γδT cells (TCRγδ⁺) as a percentage of total live CD3⁺ T cells in peripheral blood at Day 0, Day 2, and Day 7 post-ICU admission.
Day 0, Day 2, and Day 7 post-ICU admission
Change in Cytotoxic γδT Cell Proportion at Serial Time Points
Periodo de tiempo: Day 0, Day 2, and Day 7 post-ICU admission
Longitudinal flow cytometric quantification of the frequency of Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) as a percentage of total γδT cells at Day 0, Day 2, and Day 7 post-ICU admission, to track the temporal evolution of this cell subset.
Day 0, Day 2, and Day 7 post-ICU admission
Change in COX6C Expression in Cytotoxic γδT Cells at Serial Time Points
Periodo de tiempo: Day 0, Day 2, and Day 7 post-ICU admission
Longitudinal measurement of COX6C expression levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, to assess the temporal dynamics of mitochondrial metabolic gene expression.
Day 0, Day 2, and Day 7 post-ICU admission
Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and APACHE II Score
Periodo de tiempo: Day 2 post-ICU admission
Spearman rank correlation analysis between glycolytic capacity (measured by puromycin incorporation assay at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with APACHE II (Acute Physiology and Chronic Health Evaluation II) score measured within the first 48 hours of ICU admission.
Day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and SOFA Score
Periodo de tiempo: Day 2 post-ICU admission
Spearman rank correlation analysis between glycolytic capacity (measured by puromycin incorporation assay at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with SOFA (Sequential Organ Failure Assessment) score measured within the first 48 hours of ICU admission.
Day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Metabolic Parameters and vasopressor dose
Periodo de tiempo: Day 2 post-ICU admission
Correlation analysis between COX6C expression, glycolytic capacity, and mitochondrial ROS levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with vasopressor dose (reported as norepinephrine equivalent dose, NEE).
Day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Metabolic Parameters and plasma lactate levels
Periodo de tiempo: Day 2 post-ICU admission
Correlation analysis between COX6C expression, glycolytic capacity, and mitochondrial ROS levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with plasma lactate levels.
Day 2 post-ICU admission
Association Between Cytotoxic γδT Cell Glycolytic Capacity and 28-day all-cause mortality
Periodo de tiempo: Up to 90 days post-discharge
Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and 28-day all-cause mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.
Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and 90-day all-cause mortality
Periodo de tiempo: Up to 90 days post-discharge
Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and 90-day all-cause mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.
Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and in-hospital mortality
Periodo de tiempo: Up to 90 days post-discharge
Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and in-hospital mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.
Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and ICU mortality
Periodo de tiempo: Up to 90 days post-discharge
Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and ICU mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.
Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and hospital length of stay
Periodo de tiempo: Up to 90 days post-discharge
Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and hospital length of stay (days). Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.
Up to 90 days post-discharge

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

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

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

21 de junio de 2026

Finalización primaria (Estimado)

15 de abril de 2027

Finalización del estudio (Estimado)

15 de julio de 2027

Fechas de registro del estudio

Enviado por primera vez

25 de junio de 2026

Primero enviado que cumplió con los criterios de control de calidad

1 de julio de 2026

Publicado por primera vez (Actual)

2 de julio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

17 de septiembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

16 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • zjc202612

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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