Brain dendritic cells in ischemic stroke: Time course, activation state, and origin

Abstract

The immune response to stroke is comprised of inflammatory and regulatory processes. One cell type involved in both innate and adaptive immunity is the dendritic cell (DC). A DC population residing in the healthy brain (bDC) was identified using a transgenic mouse expressing enhanced yellow fluorescent protein (EYFP) under the promoter for the DC marker, CD11c (CD11c/EYFP Tg). To determine if bDC are involved in the immune response to cerebral ischemia, transient (40min) middle cerebral artery occlusion (MCAO) followed by 6, 24, or 72hr reperfusion was conducted in CD11c/EYFP Tg mice. Our results demonstrated that DC accumulated in the ischemic hemisphere at 24hr post-MCAO-reperfusion, particularly in the border region of the infarct where T lymphocytes accrued. To distinguish resident bDC from the infiltrating peripheral DC, radiation chimeras [1. wild type (WT) hosts restored with CD11c/EYFP Tg bone marrow (BM) or 2. CD11c/EYFP Tg hosts restored with WT BM] were generated and examined by immunocytochemistry. These data confirmed that DC populating the core of the infarct at 72hr were of peripheral origin, whereas those in the border region were comprised primarily of resident bDC. The brain resident (CD45 intermediate) cells of CD11c/EYFP Tg mice were analyzed by flow cytometry. Compared to microglia, bDC displayed increased major histocompatibility class II (MHC II) and co-stimulatory molecules following MCAO-reperfusion. High levels of MHC II and the co-stimulatory molecule CD80 on bDC at 72hr corresponded to peak lymphocyte infiltration, and suggested a functional interaction between these two immune cell populations.

Central Nervous System Resident Cells in Neuroinflammation: A Brave New World.

“…These cells were highly positive for the expression of the dendritic cells marker CD11c and several T cell activation-related molecules, as MHC II, CD80 and CD86. However, this was not observed early after MCAO occlusion, and thus, the initial activation observed in the CNS is most probably dependent on microglial activation rather than on bDCs (Felger JC 2010).…”

“…Concerning bDCs, is established that they are important players in the second-hit of brain and spinal cord infiltrating T CD4 cells. Using the murine model for EAE, it was demonstrated that bDCs not only present CNS-derived antigens to T cells, but they also input both Th1 and Th17 phenotype to naïve T CD4 cells (Felger JC 2010). It is interesting to remember that, as discussed in the introduction, both populations play a very relevant role in MS pathogenesis.…”

Antigen Presentation After Stroke

“…Further study is needed to clarify fully the identity and function of these DC-like brain cells. Following stroke, microglia, infiltrated macrophagesmonocytes, and DCs express MHC class II, and costimulatory molecules, thus they can act as APCs in the ischemic brain parenchyma [2,8,10]. However, antigen processing differs between macrophages and DCs, as the latter regulate lysosomal acidification better than the former in order to preserve peptides for T-cell recognition [48].…”

“…Acute brain damage generates a genuine inflammatory reaction triggered by necrotic neuronal cells that leak their content to the extracellular space and trigger strong innate immune responses involving resident microglia and infiltrating leukocytes [4,5]. Notably, antigen-presenting cells (APC) accumulate in the brain parenchyma during the days that follow experimental stroke [6][7][8][9][10]. These cells express major histocompatibility complex (MHC) class II and co-stimulatory molecules, as well as markers of conventional dendritic cells (DCs).…”

The relationship of intrathecal immunoglobulin levels with clinic symptoms and prognosis for acute phase ischemic stroke patients

“…Those proinflammatory mediators increase the blood brain barrier (BBB) disorder, which causes infiltration of leukocytes and expression of endothelial adhesion molecules [13]. MC's and DC's also contribute to the adaptive immunity by presenting antigens [12,14,15]. Through the blood-brain barrier, which has been disturbed by those pro-inflammatory mediators and chemokine, come T cells.…”