Role of regulatory T cell in clinical outcome of traumatic brain injury

Abstract

Background: Traumatic brain injury (TBI) is a life-threatening disease worldwide. Regulatory T cells (Treg cells) were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4 + cells that express CD25 and transcription factor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI.

Methods: A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University (Tianjin, China). Forty patients and 30 healthy controls were recruited from August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1, 4, 7, 14, and 21 days after TBI. Blood sample (1 ml) was withdrawn in the morning and processed within 2 h.

Results: There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1 st day after TBI. Treg level was decreased on the 4 th day, climbed up on the 7 th day and peaked on 14 th day after TBI. Treg cells declined to the normal level on 21 th day after TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4 + mononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 + mononuclear cells in the first 14 days.

Conclusions: The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.

Figure 1

Effect of blood transfusion on the levels of circulating regulatory T cells in traumatic brain injury patients.

Figure 2

Dynamic changes of circulating regulatory T cells in traumatic brain injury patients as compared to normal controls.

Figure 3

The correlation between regulatory T cells (Treg cells) and neurologic recovery. (a) The average Treg cells in survival traumatic brain injury (TBI) patients were higher than in nonsurvival TBI patients throughout the follow-up period; (b) The circulating Treg cells in survival TBI patients were significantly higher than in nonsurvival TBI patients on the 4^th day after TBI (P < 0.05); (c) The average Treg cells in TBI patients with improved conditions was higher than those with deteriorated conditions throughout the follow-up period; (d) The circulating Treg cells in TBI patients with improved conditions were significantly higher than those with deteriorated conditions on the 1^st day after TBI (P < 0.05).

Figure 4

(a) The magnitude of regulatory T cell (Treg cell) changes exhibited different trends in traumatic brain injury (TBI) patients compared with improved conditions and those with deteriorated conditions; (b) There was no significant difference in circulating Treg cells between patients with mild TBI and those with moderate and severe TBI.

Figure 5

Receiver operating characteristic curve of regulatory T cell in traumatic brain injury patients in the first 14 days.

Figure 6

Survival curve of traumatic brain injury patients with circulating regulatory T cells (Treg cells) more than 4.91% and those with circulating Treg cells <4.91% in the first 14 days.