Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations

Abstract

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients.

Patients with Chronic Spinal Cord Injury Display a Progressive Alteration over the Years of the Activation Stages of the T Lymphocyte Compartment

“…There is experimental evidence that chronic SCI is associated with systemic alterations of cellular and molecular components of the immune system, with marked involvement of T lymphocytes [19][20][21]. In addition, alterations in circulating immune cells have also been observed in patients with chronic SCI.…”

“…The expression of other molecules on the T lymphocyte membrane also allows for assessing their activation status and migratory capacity, such as the co-receptor CD28 and the chemoreceptor CCR6, respectively [17,18]. Progressively, the existence of alterations in the T lymphocyte compartment of patients with chronic SCI is being observed [19][20][21]. However, there are conflicting data regarding the distribution and activation of their CD4 and CD8 lymphocyte populations, which may be related to the limited number of patients included in the studies, the restricted and short evolutionary periods encompassed in the analyses, and the clinical heterogeneity of the patients.…”

The Role of Interleukin-10 in the Pathogenesis and Treatment of a Spinal Cord Injury

“…IL-10 inhibits the activation and proliferation of T cells, including both CD4+ and CD8+ T cells. By limiting T cell responses, IL-10 helps prevent excessive immune activation and the release of pro-inflammatory factors that can contribute to secondary injury [43]. However, IL-10 can induce regulatory T cells, leading to suppression of microglia activation, reduction in recruitment of peripheral monocytes, stabilization of local inflammatory storms, and reduction in neurodegeneration [44].…”

Effects of altered glycolysis levels on CD8+ T cell activation and function

“…Effector CD8 + T cells induce cell death by secreting cytotoxic proteins (including perforin and granzymes), which selectively trigger the activation of Caspase, leading to cell apoptosis [ 7 – 9 ]. In addition, effector CD8 + T cells also release cytokines to exert their immune function, such as tumor necrosis factor (TNF) -α, which indirectly kills target cells, and interferon (IFN) -γ, which can inhibit virus replication and enhance specific antigen presentation [ 10 , 11 ]. However, excessive cytokine may also lead to immune overactivation and threaten life [ 12 , 13 ].…”