Expression and Clinical Correlations of Costimulatory Molecules on Peripheral T Lymphocyte Subsets of Early-Stage Severe Sepsis: A Prospective Observational Study

ABSTRACT Objective: The aim of the study was to investigate the expression and clinical correlations of costimulatory molecules on peripheral T-cell subsets of severe sepsis (SS) patients. Methods: Blood samples of patients with community-acquired pneumonia-associated SS and healthy controls (HCs) were analyzed. SS patients were followed up for 28 days. Costimulatory molecule expression on T-cell subsets was determined by flow cytometry analysis. The clinical correlations of these parameters were examined. Results: A total of 92 SS patients and 29 HCs were recruited. Higher frequency of CD28, CD27, OX40 on CD4+ T cells, OX40 on CD4+CD27−CD28− T cells and lower frequency of CD4+CD27-CD28- T cells in the SS group compared with the HC group and in the nonsurvived SS group compared with the survived SS subgroup were observed. The SS group and the nonsurvived SS subgroup exhibited lower frequency of 4-1BB on either CD8+ or CD4+ T cells. The frequency of regulatory T cells (Tregs), OX40+ Tregs and 4-1BB+ conventional T cells (Tconvs) were higher in the SS group. The frequency of CD4+CD27+ T cells, CD4+CD28+ T cells, and OX40+ on CD4+CD27-CD28- T cells were positively correlated with the sequential organ failure assessment (SOFA) score. The frequency of CD4+CD27+ T cells and OX40+ on CD4+CD27−CD28− T cells independently predicted 28-day mortality. Conclusions: Early-stage SS patients exhibited an activated T-cell phenotype. Imbalanced OX40 and 4-1BB expression presented on Tregs and Tconvs may contribute to a functional imbalance of Tregs/Tconvs. The frequency of CD4+CD27+ T cells and OX40+ on CD4+CD27−CD28− T cells predicted 28-day mortality of SS.