After Injection into the Striatum, in Vitro-Differentiated Microglia- and Bone Marrow-Derived Dendritic Cells Can Leave the Central Nervous System via the Blood Stream

Abstract

The prototypic migratory trail of tissue-resident dendritic cells (DCs) is via lymphatic drainage. Since the central nervous system (CNS) lacks classical lymphatic vessels , and antigens and cells injected into both the CNS and cerebrospinal fluid have been found in deep cervical lymph nodes , it was thought that CNS-derived DCs exclusively used the cerebrospinal fluid pathway to exit from tissues. It has become evident , however , that DCs found in peripheral organs can also leave tissues via the blood stream. To study whether DCs derived from microglia and bone marrow can also use this route of emigration from the CNS , we performed a series of experiments in which we injected genetically labeled DCs into the striata of rats. We show here that these cells migrated from the injection site to the perivascular space , integrated into the endothelial lining of the CNS vasculature , and were then present in the lumen of CNS blood vessels days after the injection. Moreover , we also found these cells in both mesenteric lymph nodes and spleens. Hence , microglia-and bone marrow-derived DCs can leave the CNS via the blood stream. (Am J Pathol

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

“…Experimental and human studies have described anatomic and physiologic links between the CNS and the lymphoid tissue, via either the blood stream (10,18) or the bulk flow of cerebrospinal and interstitial fluids (2,12), that could explain our findings. Accordingly, stroke facilitated the crosstalk between the brain and the immune system, and Ags such as MBP, but not MAP2 or NR-2A, were correlated with the initial severity of stroke.…”

“…APCs and soluble Ags may leave the CNS and reach the cervical lymph nodes (CLNs) via the blood stream (10). In addition, molecules can reach the CLN by bulk flow of the intracranial fluids (11,12).…”

Experimental intracerebral vaccination protects mouse from a neurotropic virus by attracting antibody secreting cells to the CNS

“…During the memory response, small amounts of Ag can induce huge immune response, and spleen, a larger lymphoid organ than CLN in size, thus has the potential to induce huge immune response and secrete more PRV-specific Abs than CLNs, although CLNs benefit from better access to IC introduced Ag. Furthermore, IC introduced Ag and DCs could arrive at the spleen [30,33].…”

“…The delivery of soluble protein in relatively high concentrations might be a critical component of the immunogenic signal conveyed to the CLNs, and brain-derived Ag arriving in the context of CNS-resident Ag presenting cell (APC) might modulate the humoral response in CLNs [2]. Microglia or perivascular macrophages played a role as dendritic cells (DCs) to the Ag introduced into the brain, and they reached peripheral lymphoid organs such as CLNs and spleen [30,31]. 4.…”

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

“…At least three different routes of cell entry into the CNS have been described [63] but the fate of lymphocytes and macrophages once within the brain parenchyma is still controversial. They may remain in perivascular spaces, migrate through the basement membrane of the perivascular glia limitans into the CNS parenchyma and interact with target antigens [64] or simply undergo apoptosis [65].…”