Angiocentric CD3(+) T-cell infiltrates in human immunodeficiency virus type 1-associated central nervous system disease in children

A significant proportion of brain tissue specimens from children with AIDS show evidence of vascular inflammation in the form of transmural and/or per ivascular mononuclear-cell infiltrates at autopsy. Previous studies have sh own that in contrast to inflammatory lesions observed in human immunodefici ency virus type 1 (HIV-1) encephalitis, in which monocytes/macrophages are the prevailing mononuclear cells, these infiltrates consist mostly of lymph ocytes. Perivascular mononuclear-cell infiltrates were found in brain tissu e specimens collected at autopsy from five of six children with AIDS and co nsisted of CD3(+) T cells and equal or greater proportions of CD68(+) monoc ytes/macrophages. Transmural (including endothelial) mononuclear-cell infil trates were evident in one patient and comprised predominantly CD3(+) T cel ls and small or, in certain vessels, approximately equal proportions of CD6 8(+) monocytes/macrophages. There was a clear preponderance of CD3(+) CD8() T cells on the endothelial side of transmural infiltrates. In active lesi ons of transmural vasculitis, CD3(+) T-cell infiltrates exhibited a distinc tive zonal distribution. The majority of CD3(+) cells were also CD8(+) and CD45RO(+). Scattered perivascular monocytes/macrophages in foci of florid v asculitis were immunoreactive for the p24 core protein. In contrast to the perivascular space, the intervening brain neuropil was dominated by monocyt es/macrophages, microglia, and reactive astrocytes, containing only scant C D3(+) CD8(+) cells. Five of six patients showed evidence of calcific vascul opathy, but only two exhibited HIV-1 encephalitis. One patient had multiple subacute cerebral and brainstem infarcts associated with a widespread, ful minant mononuclear-cell vasculitis. A second patient had an old brain infar ct associated with fibrointimal thickening of large leptomeningeal vessels. These infiltrating CD3(+) T cells may he responsible for HN-l-associated C NS vasculitis and vasculopathy and for endothelial-cell injury and the open ing of the blood-brain barrier in children with AIDS.