title: Angiocentric CD3(+) T-cell infiltrates in human immunodeficiency virus type 1-associated central nervous system disease in children.
abstract: A significant proportion of brain tissue specimens from children with AIDS show evidence of vascular inflammation in the form of transmural and/or perivascular mononuclear-cell infiltrates at autopsy. Previous studies have shown that in contrast to inflammatory lesions observed in human immunodeficiency virus type 1 (HIV-1) encephalitis, in which monocytes/macrophages are the prevailing mononuclear cells, these infiltrates consist mostly of lymphocytes. Perivascular mononuclear-cell infiltrates were found in brain tissue specimens collected at autopsy from five of six children with AIDS and consisted of CD3(+) T cells and equal or greater proportions of CD68(+) monocytes/macrophages. Transmural (including endothelial) mononuclear-cell infiltrates were evident in one patient and comprised predominantly CD3(+) T cells and small or, in certain vessels, approximately equal proportions of CD68(+) monocytes/macrophages. There was a clear preponderance of CD3(+) CD8(+) T cells on the endothelial side of transmural infiltrates. In active lesions of transmural vasculitis, CD3(+) T-cell infiltrates exhibited a distinctive zonal distribution. The majority of CD3(+) cells were also CD8(+) and CD45RO+. Scattered perivascular monocytes/macrophages in foci of florid vasculitis were immunoreactive for the p24 core protein. In contrast to the perivascular space, the intervening brain neuropil was dominated by monocytes/macrophages, microglia, and reactive astrocytes, containing only scant CD3(+) CD8(+) cells. Five of six patients showed evidence of calcific vasculopathy, but only two exhibited HIV-1 encephalitis. One patient had multiple subacute cerebral and brainstem infarcts associated with a widespread, fulminant mononuclear-cell vasculitis. A second patient had an old brain infarct associated with fibrointimal thickening of large leptomeningeal vessels. These infiltrating CD3(+) T cells may be responsible for HIV-1-associated CNS vasculitis and vasculopathy and for endothelial-cell injury and the opening of the blood-brain barrier in children with AIDS.
authors.affiliation: Department of Microbiology and Immunology, St. Christopher's Hospital for Children and Allegheny University of the Health Sciences, Philadelphia, Pennsylvania, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Katsetos
authors.forename: J E
authors.initials: JE
authors.lastname: Fincke
authors.forename: A
authors.initials: A
authors.lastname: Legido
authors.forename: H W
authors.initials: HW
authors.lastname: Lischner
authors.forename: J P
authors.initials: JP
authors.lastname: de Chadarevian
authors.forename: E M
authors.initials: EM
authors.lastname: Kaye
authors.forename: C D
authors.initials: CD
authors.lastname: Platsoucas
authors.forename: E L
authors.initials: EL
authors.lastname: Oleszak
mesh_terms: D015526:AIDS Dementia Complex / Q000276:immunology* / Q000473:pathology*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015497:HIV-1; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D014657:Vasculitis / Q000276:immunology / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C067980:CD68 antigen, human; D000097382:CD68 Molecule