Ultrastructural Location of Major Histocompatibility Complex (MHC) Class II Positive Perivascular Cells in Histologically Normal Human Brain

Abstract

The expression of major histocompatibility complex (MHC) class I and II antigens was studied in surgical and postmortem brain biopsy tissue using light and electron microscopic immunocytochemistry. In addition, monoclonal antibodies directed against human macrophages (EBM11) and alpha-smooth muscle actin were applied. It is shown that blood vessel-associated MHC class II immunoreactivity in histologically normal human brain can be localized to a distinct class of cells, termed perivascular cells, which share macrophage but not smooth muscle cell antigen. This immunophenotype, the location in the perivascular space as well as the morphology, frequency and tissue distribution distinguish perivascular cells from pericytes and intraparenchymal microglia. It is suggested that MHC class II positive perivascular cells are a normal constituent of the human cerebral microvasculature. The potential role of these cells in immunological reactions occurring at the blood-brain interface is discussed.

Microglial Phenotypes and Functions in Multiple Sclerosis

“…Competent antigen presentation is dependent on cells expressing both the requisite MHC and costimulatory molecules. Perivascular macrophages were considered the main APC at the level of the BBB because in both humans and rodents they constitutively express MHC class II (Lassmann et al 1991;Graeber et al 1992) and their expression is up-regulated in MS lesions (Bo et al 1994). …”

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

“…5;, then reported as perivascular microglial cells in 1986 by Hickey and Kimura (15), or ED2-positive perivascular cells in 1989 by Graeber et al. (16,17). To (22,23 (Fig.…”

“…Morphologically, the barrier is attributed to the continuous tight junctions between endothelial cells. In addition to the existence of a barrier function of capillary endothelial cells, accumulating evidence suggests the involvement of a specific type of cell in the barrier and scavenger functions in brain blood vessels (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Exogenous macromolecules injected into blood vessels or cerebral ventricles accumulated in a specific type of perivascular cell.…”

Blood-Brain Barrier Disruption and Encephalitis in Animal Models of AIDS

“…Immediately subjacent to the endothelial cells, and anchoring them to the underlying tissues, is the basement membrane which is composed largely of Type IV collagen and laminin. Perivascular macrophages and the foot processes of astrocytes and microglia surround the endothelial cells (Hickey and Kimura, 1988, Graeber et al, 1992, Streit and Graeber, 1993, Lassmann et al, 1991. Tight junctions are a fibrillary network of transmembrane proteins that can be phosphorylated to regulate physiologic processes such as replacement of perivascular macrophages by circulating monocytes.…”