PMID- 35898496
OWN - NLM
STAT- MEDLINE
DCOM- 20220729
LR  - 20220822
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Early Expression of Functional Markers on CD4(+) T Cells Predicts Outcomes in ICU 
      Patients With Sepsis.
PG  - 938538
LID - 10.3389/fimmu.2022.938538 [doi]
LID - 938538
AB  - OBJECTIVE: There is evidence that metabolic disorder, dysfunction and abnormal 
      apoptosis of immune cells are closely related to immunosuppression in sepsis. 
      Single monitoring of exhaustion receptors does not reflect well the immune status 
      of septic patients; therefore, we monitored immune status in relation to 
      metabolism, function and apoptosis of immune cells to find good prognostic 
      indicators for sepsis. DESIGN: A single-center prospective observational study. 
      SETTING: Teaching hospital including an academic tertiary care center. PATIENTS: 
      81 patients with sepsis and 22 without sepsis admitted to the ICU. INTERVENTIONS: 
      Patients were divided according to Sequential Organ Failure Assessment (SOFA) 
      score: mild sepsis 2-5 points and severe sepsis >/=6 points. SOFA score was 
      recalculated daily. If it changed by >/=2 points within 2 days, T-cell metabolism, 
      function and apoptotic makers [mammalian target of rapamycin (mTOR), T-bet, 
      interferon (IFN)-gamma, granzyme B, and programmed cell death (PD)-1] were 
      continuously monitored on days 1, 3 and 5 after admission. MEASUREMENTS AND MAIN 
      RESULTS: The overall status of immune cells was compared among patients with 
      different severity of sepsis. Patients with severe sepsis, compared with mild and 
      no sepsis, had lower lymphocyte counts, higher expression of receptors associated 
      with cell metabolism, activation and apoptosis, and lower expression of 
      functional receptors. Multivariate regression analysis revealed that frequency of 
      CD4(+) T cells expressing mTOR, IFN-gamma and PD-1 at admission was an independent 
      predictor of 28-day mortality. Receiver operating characteristic curve analysis 
      indicated that frequency of CD4(+) T cells expressing mTOR, IFN-gamma and PD-1 
      predicted 28-day mortality, with cutoffs of 30.57%, 12.81% and 22.46%, 
      respectively. The expression of related receptors on CD8+ T cells showed similar 
      trend to that on CD4+ T cells, but no significant difference was found. 
      CONCLUSIONS: Abnormally increased expression of metabolic and apoptotic receptors 
      on CD4(+) T cells and decreased expression of functional factors are associated 
      with poor prognosis in ICU patients with sepsis. Poor prognosis can be identified 
      by early detection of expression of mammalian target of rapamycin (mTOR), IFN-gamma 
      and PD-1 on CD4(+) T cells.
CI  - Copyright (c) 2022 Chen, Wang, Guo, Li and Cui.
FAU - Chen, Jianwei
AU  - Chen J
AD  - Department of Critical Care Medicine, State Key Laboratory of Complex Severe and 
      Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Science and Peking Union Medical College, Beijing, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Critical Care Medicine, Beijing Jishuitan Hospital, Beijing, China.
FAU - Guo, Ran
AU  - Guo R
AD  - Department of Critical Care Medicine, State Key Laboratory of Complex Severe and 
      Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Science and Peking Union Medical College, Beijing, China.
FAU - Li, Haolong
AU  - Li H
AD  - Department of Critical Care Medicine, State Key Laboratory of Complex Severe and 
      Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Science and Peking Union Medical College, Beijing, China.
FAU - Cui, Na
AU  - Cui N
AD  - Department of Critical Care Medicine, State Key Laboratory of Complex Severe and 
      Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Science and Peking Union Medical College, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20220711
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Biomarkers
MH  - CD4-Positive T-Lymphocytes/metabolism
MH  - Humans
MH  - Intensive Care Units
MH  - Lymphocyte Count
MH  - *Programmed Cell Death 1 Receptor
MH  - *Sepsis/metabolism
MH  - TOR Serine-Threonine Kinases
PMC - PMC9309518
OTO - NOTNLM
OT  - IFN-gamma
OT  - PD-1
OT  - T-cell function
OT  - mTOR
OT  - sepsis induced immunosuppression
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/29 06:00
MHDA- 2022/07/30 06:00
PMCR- 2022/01/01
CRDT- 2022/07/28 02:09
PHST- 2022/05/07 00:00 [received]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/07/28 02:09 [entrez]
PHST- 2022/07/29 06:00 [pubmed]
PHST- 2022/07/30 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.938538 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jul 11;13:938538. doi: 10.3389/fimmu.2022.938538. eCollection 
      2022.