Angiocentric CD3+ T-Cell Infiltrates in HIV-1-Associated CNS Disease in Children




C.D. Katsetos1, J.E. Fincke1, A. Legido2,

H.W. Lischner2, J.-P Chadarevian3, E.M. Kaye2, C.D. Platsoucas1,

and E.L.Oleszak4*. 1Department

Microbiology & Immunology, Fels Institute of Cancer Research

& Molecular Biology; 2Temple

University School of Medicine, Department of Pediatrics; 3Department

Anatomic Pathol. St. Christopher’s Hosp Children, Allegheny

University; 4Department Anatomy &

Cell Biology and Neurology, Temple University School of Medicine.

A substantial proportion of

brains examined at autopsy from children with AIDS show evidence

of mononuclear cell infiltration. Previous studies have shown

that these infiltrates are composed primarily of

monocytes/macrophages. We report here the presence of

angiocentric infiltrates comprised primarily of T cells in the

brains of children with AIDS. Perivascular infiltrates were found

in autopsy specimens from 5 of 6 children with AIDS and consisted

of CD3+ T-cells and in some cases, equal or greater proportions

of CD68+ monocytes/macrophages. Transmural mononuclear cell

infiltrates were found in one patient that consisted primarily of

CD3+ T cells, with an almost equal amount of CD68+ monocyte/

macrophages found only in certain vessels. There was a clear

majority of CD3+ T cells on the endothelial side of transmural

infiltrates. The majority of these cells were also CD8+ and

CD45R0+. The intervening brain neuropil, however, was dominated

by monocytes/macrophages/microglia, and reactive astrocytes with

very few CD3+/CD8+ cells present. Five of six patients showed

evidence of calcific vasculopathy, with only two exhibiting

HIV-1-encephalitis. One patient had multiple infarcts indicative

of a widespread mononuclear cell vasculitis. A second patient had

an old infarct associated with fibrointimal thickening of the

leptomeningeal vessels. These infiltrating T cells may be

responsible for HIV-1 associated CNS vasculitis and vasculopathy,

for endothelial cell injury, and for comprising the

blood-brain-barrier in children with AIDS.