Abstract
Stroke-induced immunodepression (SIID) results when T cell and non-T immune cells, such as B cells, NK cells and monocytes, are reduced in the peripheral blood and spleen after stroke. We investigated the hypothesis that T cells are required for the reductions in non-T cell subsets observed in SIID, and further examined a potential correlation between lymphopenia and High-mobility group protein B1 (HMGB1) release, a protein that regulates inflammation and immunodepression. Our results showed that focal ischemia resulted in similar cortical infarct sizes in both wild type (WT) Sprague Dawley (SD) rats and nude rats with a SD genetic background, which excludes the possibility of different infarct sizes affecting SIID. In addition, the numbers of CD68-positive macrophages in the ischemic brain did not differ between WT and nude rats. Numbers of total peripheral blood mononuclear cells (PBMCs) or splenocytes and lymphocyte subsets, including T cells, CD4+ or CD8+ T cells, B cells and monocytes in the blood and spleen, were decreased after stroke in WT rats. In nude rats, however, the total number of PBMCs and absolute numbers of NK cells, B cells and monocytes were increased in the peripheral blood after stroke; nude rats are athymic therefore they have few T cells present. Adoptive transfer of WT splenocytes into nude rats before stroke resulted in lymphopenia after stroke similar to WT rats. Moreover, in vitro T cell proliferation stimulated by Concanavalin A was significantly inhibited in WT rats as well as in nude rats receiving WT splenocyte adoptive transfer, suggesting that T cell function is indeed inhibited after stroke. Lastly, we demonstrated that stroke-induced lymphopenia is associated with a reduction in HMGB1 release in the peripheral blood. In conclusion, T cells are required for stroke-induced reductions in non-T immune cells and they are the most crucial lymphocytes for SIID.
Highlights
Stroke-induced immunodepression (SIID) results in infection, which is considered to be the major complication leading to delayed mortality in stroke patients [1,2,3,4]
As infarct size and location may affect the degree of SIID in wild type (WT) rats alone, this result indicates that the potential difference in SIID between WT and nude rats revealed in this study is due to T cells rather than infarct size or location
Ours is the first report to demonstrate that stroke increases total peripheral blood mononuclear cells (PBMCs) as well as B cells, NK cells and monocytes in T-celldeficient nude rats
Summary
Stroke-induced immunodepression (SIID) results in infection, which is considered to be the major complication leading to delayed mortality in stroke patients [1,2,3,4]. A SIID hallmark is lymphopenia, which is characterized by decreased immune cells in the peripheral blood and spleen [4,5]. Thereafter, strong evidence from clinical studies has shown that stroke causes a reduction of T cells in the peripheral blood and inhibition of T cell proliferation in response to antigen stimulation, as well as inhibition of the delayed type hypersensitivity (DTH) skin test [7]. Urra et al reported that B cells in stroke patients were reduced [12], whereas Vogelgesang et al reported they were unchanged [10]. An early study of stroke patients suggests that IgM and IgG immunoglobulins were unchanged but IgA was increased [7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call