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GammaDelta T-Cells Are Differentially Activated in Geriatric Septic Patients
*Daithi S Heffernan, *Sean F Monaghan, *Shiang Chung, *Mai L Tran, *Stefan Gravenstein, William G Cioffi, *Alfred Ayala
Brown University, Providence, RI

Objective: Sepsis is associated with lymphocyte loss and dysfunction. Regulatory T-cell populations are critical modulators of the immune response. GammaDelta-T-cells (GDT-cells) modulate both pro- and counter- inflammatory responses to sepsis. GDT-cells are critical to proper patient responses to sepsis. Geriatric patients display baseline numeric and functional decline in immune drivers. However, no data currently addresses GDT-cell changes in septic geriatric patients.
Design:White cell count was available from daily lab draws. Whole blood was stained with monoclonal antibodies against anti-CD3+ (Lymphocytes), anti-TCR-PAN gammadelta (GammaDeltaT-cells) and CD69 (marker of early cell activation). Flow cytometry calculated both percentage and absolute cell counts. Blood from 10 healthy volunteers was also collected.
Setting:Level 1 Tertiary referral center
Patients:27 young (18-35yrs) and 51 geriatric (>/=65yrs) critically ill patients with microbiologically confirmed sepsis
Interventions:Observational
Main Outcome Measures:Percentage and absolute number of CD3+, GDT-cells, activation status between young and geriatric septic patients
Results:Septic patients, compared with healthy controls, displayed a marked leukocytosis (14.4 vs 6.4x10^9/L;p=0.001) and decreased CD3+lymphocytes (7.4% vs 26.1%;p=0.001). Compared to controls, septic patients displayed decreased percentage of GDT-cells (3.3+/-0.37% vs 5.4+/-0.9%;p=0.046) but increased activated CD69+GDT-cells (23.6+/-3.1 vs 4.8+/-0.5%;p=0.002). Comparing geriatric to young patients, there was no difference in percentage GDT-cells (3.2+/-0.5% vs3.5+/-0.5;p=0.7), absolute GDT-cells (3.7+/-0.9 vs 3.1+/-0.4x10^7/L;p=0.42), or activated GDT-cells (22+/-3.2% vs 24.7+/-3.1%;p=0.58). Among Geriatric patients, those who died had sginificantly more activated GDT-cells than those who lived (31.5+/-4.4 vs 16.7+/-3.2%;p=0.02)
Conclusions: Despite known baseline differences between geriatric and young individuals, there is no difference in GDT-cell populations among septic patients. The noted increased activation of GDT-cells in geriatric patients who died most likely reflects exhausted target cells (neutrophils or macrophages) necessitating increased (but ineffective) activated regulators such as GammaDelta-T-cells.


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