Abnormal Characterization and Distribution of Circulating Regulatory T Cells in Patients with Chronic Spinal Cord Injury According to the Period of Evolution

SIMPLE SUMMARY: Immune dysfunction is a major feature of chronic spinal cord injuries (SCIs). It is associated with many of the complications observed in these patients, such as increased vulnerability to infections and other medical challenges. The role of regulatory T cells (Tregs) after SCI is beginning to be more acutely understood; however, little is known about their implications at chronic stages. By using flow cytometry, we characterized circulating Tregs from chronic SCI patients according to the time of initial injury (1–5 years; 5–15 years; and >15 years). Our results demonstrate significant changes in the immunological phenotypes of these cells, especially in patients with long periods of evolution (5–15 years and >15 years with chronic SCI). Despite the fact that a deeper understanding of the immune dysfunction caused by chronic SCI is still required, the characterization of circulating leukocytes such as Tregs and other populations can open up the possibility of finding translational biomarkers or therapeutic approaches that may aid in the clinical management of chronic SCI. ABSTRACT: Spinal cord injury (SCI) is a progressive and complex neurological disorder accompanied by multiple systemic challenges. Peripheral immune dysfunction is a major event occurring after SCI, especially in its chronic phase. Previous works have demonstrated significant changes in different circulating immune compartments, including in T cells. However, the precise characterization of these cells remains to be fully unraveled, particularly when considering important variants such as the time since the initial injury. In the present work, we aimed to study the level of circulating regulatory T cells (Tregs) in SCI patients depending on the duration of evolution. For this purpose, we studied and characterized peripheral Tregs from 105 patients with chronic SCI using flow cytometry, with patients classified into three major groups depending on the time since initial injury: short period chronic (SCI-SP, <5 years since initial injury); early chronic (SCI-ECP, from 5–15 years post-injury) and late chronic SCI (SCI-LCP, more than 15 years post-injury. Our results show that both the SCI-ECP and SCI-LCP groups appeared to present increased proportions of CD4+ CD25+/low Foxp3+ Tregs in comparison to healthy subjects, whereas a decreased number of these cells expressing CCR5 was observed in SCI-SP, SCI-ECP, and SCI-LCP patients. Furthermore, an increased number of CD4+ CD25+/high/low Foxp3 with negative expression of CD45RA and CCR7 was observed in SCI-LCP patients when compared to the SCI-ECP group. Taken together, these results deepen our understanding of the immune dysfunction reported in chronic SCI patients and how the time since initial injury may drive this dysregulation.