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90th Annual Meeting Abstracts

A Divergent response of Innate Regulatory T-cells to sepsis in Humans. CIrculating Invariant Natural Killer T-cells are preserved
*Daithi S. Heffernan, MD AFRCSI1, *Chun-Shiang Chung, PhD2, *Fabienne Venet, PhD2, *Radhika Ravindran, BS2, *Mai Tran, BS2, William G Cioffi, MD1, *Alfred Ayala, PhD2
1Brown University, Division of Surgical Research, Rhode Island Hospital, Providence, RI;2Division of Surgical Research, Rhode Island Hospital, Providence, RI

Objective: Sepsis is associated with immunosuppression, especially T-lymphocytes and the GammaDelta (γδ) subpopulation. However, the invariant Natural Killer T-cell (iNKT-cells) subpopulation has been shown to be important in regulating macrophage function; ie, bacterial clearance and survival following sepsis. We hypothesized that iNKT-cells would be preserved in sepsis despite a suppression of other T-lymphocytes.
Design: A cohort study of ICU patients with sepsis compared with normal healthy controls.
Setting: Adult Trauma and Surgical Intensive Care Units at a university hospital/level 1 trauma center.
Patients: 32 septic patients compared with 10 healthy volunteers.
Interventions: Blood was collected from patients at the time of daily lab draws in the ICU. Daily white cell count was recorded. Flow cytometry was used to detect monoclonal antibodies to CD3, anti-TCR PAN-γδ, and anti-TCR-Vα-24 (invariant Natural Killer T-cells).
Main Outcome measures: Both percentage and absolute number of circulating CD3+ Lymphocytes, γδT-cells and iNKT-cells in septic patients compared to healthy controls.
Results: Septic patients had decreased percentage (7.3% vs 26.1%; p=0.0005) and absolute number (9.29x10exp8/L vs 15.84x10exp8/L; p=0.007) of CD3-Lymphocytes. γδT-cells were also noted to be reduced in both percentage (1.9% vs 5.1%; p=0.00004) and absolute number (2.15x10exp7/L vs 7.5x10exp7/L; p=0.00004) compared with healthy controls.
However, iNKT-cells as a percentage of CD3 cells was increased in septic patients (0.739% vs 0.565%; p=0.0049) leading to a preservation of the absolute number of iNKT-cells (6.64x10exp6/L vs 8.86x10exp6/L; p=0.22) in septic patients.
Conclusions: In keeping with previous observations, sepsis is associated with a general Lymphocyte loss. However, a divergence appears within the innate regulatory T-cells with preservation of the iNKT-cell subpopulation. This would suggest a key role in the septic response for invariant Natural Killer T-Lymphocytes.


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