Traffic of antigen presenting cells to and from the brain

In the normal healthy rodent brain, there are no dendritic cells. However, following acute brain injury, and in immune mediated lesions, small numbers of OX62+ve dendritic cells appear in the rat brain parenchyma. To investigate the origin of these cells, rats with acute excitotoxic lesions were subjected to a number of different manipulations. Depletion of the ED2+ perivascular macrophages by intracerebroventricular injection of chlodronate liposomes did not prevent the appearance of OX62+ve cells in the parenchyma, but bone marrow depletion by whole body irradiation abrogated their appearance. Thus, the OX62+ve cells are derived from blood and not transformation of resident cell populations. To investigate whether potential antigen presenting cells in the brain parenchyma, such as the perivascular cells, traffic from brain to the peripheral immune system fluorescent microspheres approximating the size of a virus (0.02 micrometre) or a bacterium (1.00 micrometre) were microinjected into distinct brain compartments. Injection into the meninges or ventricles led to the appearance of the fluorescent microspheres in the cervical lymph nodes and the liver. In contrast no fluorescent microspheres were found peripherally following injections restricted to the parenchyma. The microspheres were observed within perivascular macrophages. A local inflammatory response within the brain resulted in a dramatic alteration of the distribution of microspheres delivered to the parenchyma