Reduced Efficacy of Circulating Costimulatory Cells After Focal Cerebral Ischemia

Abstract

Background and Purpose-Cerebral ischemia is ensued by a cellular immune depression syndrome. The postischemic functional capacity of T lymphocytes is controversial, and interactions between leukocyte subsets are largely unknown. Understanding the immunologic interplay between antigen-presenting cells and lymphocytes as well as between distinct lymphocyte subsets after stroke might be of clinical/therapeutic significance because animal data argue for a cerebroprotective effect of, for example, CD4ϩCD25ϩ regulatory T cells. Methods-Ex vivo CD4ϩ T cell proliferation was analyzed in experimental and human stroke using fluorescence activated cell sorter analysis. To investigate suppressive effects of CD4ϩCD25ϩ regulatory T cells as well as the influence of costimulatory cells on CD4ϩ T cell proliferation, subsets were magnetically sorted before proliferation assay setup. Results-After stroke: (1) proliferation of mouse and human CD4ϩ T cells on T cell receptor stimulation was unaltered;(2) the suppressive effect of CD4ϩCD25ϩ regulatory T cells in mouse and man was unaltered; and (3)

Molecular dialogs between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

“…However, these studies also indicated a role for the original brain DCs in post-ischemic neuroinflammation. A significant decrease in circulating DC precursors (Yilmaz and Granger, 2010) after human or experimental stroke has been reported, likely reflecting the reduced co-stimulatory efficacy of circulating cells (Hug et al, 2011). These results suggest that peripheral DCs are recruited from the blood into the ischemic brain, possibly acting either to trigger post-ischemic cerebral immune reactions or inducing systemic immunosuppression.…”

“…With regard to cell function, it was recently reported that the suppressive effect of Tregs was unaltered after stroke in mice and humans (Hug et al, 2011). Thus, an increase in the number of Tregs, rather than an enhancement of the function of each cell, may be responsible for endogenous immunosuppression after stroke.…”

Changes in the cellular immune system and circulating inflammatory markers of stroke patients

“…Some research has shown that regulatory T (Treg) cells, interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-β contribute to the process of immunodepression [9–11]. Moreover, TGF-β and IL-10 are essential for the differentiation of Treg cells [12].…”

Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art

“…However, also antigen-presenting cells (APCs) in peripheral blood should give important insight on immune response to stroke and the mechanism of tolerance [193]. During cerebral focal ischemia a reduced peripheral costimulatory activity has been observed [194]. Stroke generates imbalance in the acquired immune response and a decrease in circulating dendritic cells [195].…”