An observational study in Sepsis, Critical Illness and Immunosuppression, sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Observational
This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδ T cells in critically ill patients with and without sepsis. As a bridge between innate and adaptive immunity, γδ T cells contribute to early antimicrobial defense; however, their cytotoxic function and its metabolic regulation in sepsis remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed altered expression of cytotoxicity-associated genes (GZMB, PRF1, and GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes in cytotoxic γδ T cells from patients with sepsis. In particular, COX6C expression correlated with cytotoxic effector gene expression. Across healthy volunteers, critically ill non-septic patients, and critically ill septic patients, we will integrate flow cytometry, mitochondrial function assays, and functional validation experiments to characterize circulating cytotoxic γδ T-cell abundance and function and examine the contribution of COX6C to mitochondrial dysfunction and impaired cytotoxicity.
To investigate the relationship between systemic tryptophan metabolism and these cellular abnormalities, targeted tryptophan-pathway metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) will quantify kynurenic acid (KYNA), tryptophan, kynurenine, and related metabolites in paired peripheral blood and fecal samples. Patients with sepsis will be stratified into older (≥65 years) and non-older (\<65 years) groups and compared with age-matched healthy volunteers, with critically ill non-septic patients providing an additional disease control group. Metabolite concentrations and pathway-related ratios will be analyzed in relation to cytotoxic γδ T-cell abundance, cytotoxic function, mitochondrial OXPHOS, and COX6C expression, accounting for renal function, disease severity, antibiotic exposure, and nutritional support. These analyses will assess whether age-associated alterations in tryptophan metabolism, particularly KYNA, are associated with cytotoxic γδ T-cell dysfunction and identify candidate metabolic mechanisms for subsequent validation.
2,416 studies on the registry are indexed under Sepsis; 541 are open to participants now.
This study's planned enrollment of 105 is below the median of 150 across 1,162 observational studies indexed under Sepsis.
Browse Sepsis studies →Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is the lead sponsor of 181 studies on the registry; 144 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Healthy Control Group (NHC):
Non-septic Critical Illness Group (CI-NS):
Septic Critical Illness Group (CI-Sep):
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
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.
Time frame: Within day 2 post-ICU admission
Change in COX6C Expression in Cytotoxic γδT Cells
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).
Time frame: Within day 2 post-ICU admission
Blood Kynurenic Acid Level
Peripheral blood KYNA concentration will be quantified using targeted tryptophan-pathway metabolomics by LC-MS/MS and compared among older patients with sepsis (≥65 years), non-older adult patients with sepsis (\<65 years), and healthy volunteers.
Time frame: Within day 2 post-ICU admission
Fecal Kynurenic Acid Level
Fecal KYNA concentration will be quantified using targeted tryptophan-pathway metabolomics by LC-MS/MS and compared among older patients with sepsis (≥65 years), non-older adult patients with sepsis (\<65 years), and healthy volunteers.
Time frame: Within day 2 post-ICU admission
Blood Kynurenic Acid Levels and Their Associations With Cytotoxic γδ T-Cell Function
Associations between peripheral blood KYNA concentrations, quantified by targeted LC-MS/MS, and prespecified quantitative measures of cytotoxic γδ T-cell function will be assessed in older patients with sepsis (≥65 years), non-older adult patients with sepsis (\<65 years), and healthy volunteers.
Time frame: Within day 2 post-ICU admission
Fecal Kynurenic Acid Levels and Their Associations With Cytotoxic γδ T-Cell Function
Associations between fecal KYNA concentrations, quantified by targeted LC-MS/MS, and prespecified quantitative measures of circulating cytotoxic γδ T-cell function will be assessed in older patients with sepsis (≥65 years), non-older adult patients with sepsis (\<65 years), and healthy volunteers.
Time frame: Within day 2 post-ICU admission
Change in Cytotoxic Molecule Expression in Cytotoxic γδT Cells
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⁺).
Time frame: Within day 2 post-ICU admission
Change in Mitochondrial Mass in Cytotoxic γδT Cell
Flow cytometric quantification of mitochondrial mass using MitoTracker Green FM staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Time frame: Within day 2 post-ICU admission
Change in Mitochondrial Membrane Potential (TMRE) in Cytotoxic γδT Cells
Flow cytometric quantification of mitochondrial membrane potential using tetramethylrhodamine ethyl ester (TMRE) staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Time frame: Within day 2 post-ICU admission
Change in Mitochondrial Membrane Potential (JC-1) in Cytotoxic γδT Cells
Flow cytometric quantification of mitochondrial membrane potential using JC-1 dye (red/green fluorescence ratio) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Time frame: Within day 2 post-ICU admission
Change in Oxygen Consumption Rate (OCR) in Cytotoxic γδT Cells
Measurement of basal oxygen consumption rate reflecting oxidative phosphorylation (OXPHOS) capacity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Time frame: Within day 2 post-ICU admission
Change in Extracellular Acidification Rate (ECAR) in Cytotoxic γδT Cells
Measurement of basal extracellular acidification rate reflecting glycolytic metabolic activity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).
Time frame: Within day 2 post-ICU admission
Change in Glycolytic Capacity of Cytotoxic γδT Cells at Serial Time Points
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.
Time frame: Day 0, Day 2, and Day 7 post-ICU admission
Change in Mitochondrial ROS Levels in Cytotoxic γδT Cells at Serial Time Points
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.
Time frame: Day 0, Day 2, and Day 7 post-ICU admission
Change in Cytotoxic γδT Cell Migratory Function
Assessment of Cytotoxic γδT cell (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) chemotactic and migratory capacity using Transwell migration assay.
Time frame: Within day 2 post-ICU admission
Change in Total γδT Cell Proportion at Serial Time Points
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.
Time frame: Day 0, Day 2, and Day 7 post-ICU admission
Change in Cytotoxic γδT Cell Proportion at Serial Time Points
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.
Time frame: Day 0, Day 2, and Day 7 post-ICU admission
Change in COX6C Expression in Cytotoxic γδT Cells at Serial Time Points
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.
Time frame: Day 0, Day 2, and Day 7 post-ICU admission
Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and APACHE II Score
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.
Time frame: Within day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and SOFA Score
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.
Time frame: Within day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Metabolic Parameters and vasopressor dose
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).
Time frame: Within day 2 post-ICU admission
Correlation Between Cytotoxic γδT Cell Metabolic Parameters and plasma lactate levels
Correlation analysis between COX6C expression, glycolytic capacity, and mitochondrial ROS levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with plasma lactate levels.
Time frame: Within day 2 post-ICU admission
Association Between Cytotoxic γδT Cell Glycolytic Capacity and 28-day all-cause mortality
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.
Time frame: Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and 90-day all-cause mortality
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.
Time frame: Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and in-hospital mortality
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.
Time frame: Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and ICU mortality
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.
Time frame: Up to 90 days post-discharge
Association Between Cytotoxic γδT Cell Glycolytic Capacity and hospital length of stay
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.
Time frame: Up to 90 days post-discharge
Started Jun 2026 (actual). Primary completion is estimated for Apr 2027, 9 months after the start.
Of 491 non-industry observational studies under Sepsis, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 58. This study's planned 9 months is below that.
Counting every sponsor, half of 543 studies reached it within 27 months; a quarter within 12 and three quarters within 56.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology →