B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients

作者：Nicholas J. Shubin, Sean F. Monaghan, Daithi S. Heffernan, Chun‐Shiang Chung, Alfred Ayala · 发表于：Critical Care · 年份：2013 · DOI：10.1186/cc13131 · 被引用次数：96 · 研究领域：Sepsis Diagnosis and Treatment、Phagocytosis and Immune Regulation、Immune Cell Function and Interaction

INTRODUCTION: Sepsis is a deadly inflammatory condition that often leads to an immune suppressed state; however, the events leading to this state remain poorly understood. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to effectively inhibit CD4+ T-cell function. Therefore, our objectives were to determine: 1) if lymphocyte BTLA expression was altered in critically ill patients and experimentally induced septic mice, 2) whether augmented CD4+ T-cell BTLA expression was associated with poor septic patient outcomes, and 3) if BTLA expression affected the CD4+ T-cell apoptotic cell loss observed in the lymphoid organs of septic mice. METHODS: Changes in CD4+ lymphocyte BTLA expression were compared with morbid event development in critically ill ICU patients (11 septic and 28 systemic inflammatory response syndrome subjects). Wild type and BTLA gene deficient mice were utilized to evaluate the expression and role of BTLA in septic lymphocyte apoptotic cell loss. RESULTS: The observed septic ICU patients had a significantly higher percentage of peripheral blood BTLA+ CD4+ lymphocytes compared with critically ill non-septic individuals. Moreover, the non-septic patients with CD4+ T-cells that were greater than 80% BTLA+ were more susceptible to developing nosocomial infections. Additionally, in general, critically ill patients with CD4+ T-cells that were greater than 80% BTLA+ had longer hospital stays. Comparatively, circulating CD4+ T-cell and B-cell...