Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome

CD8+ T cells infiltrate brains with human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE) and related animal models; their perineuronal localization suggests cytotoxic T cell (CTL)-mediated neuronal killing. Because CTLs have not been identified in acquired immunodeficiency syndrome ( AIDS) brains, the authors identified their cytotoxic granules in autopsy AIDS brains with HIVE and without HIVE (HIVnE) plus controls (7 to 13 cases/group) and determined gene expression profiles of CTL-associated genes in a separate series of cases. CD3+ and CD8+ T cells were significantly increased (P < .01) in perivascular spaces and inflammatory nodules in HIVE but were rare or absent in brain parenchyma in HIVnE and control brains. Eight HIVE brains contained granzyme B+T cells and five contained perforin+ T cells. Their T-cell origin was confirmed by colocalization of CD8 and granzyme B in the same cell and the absence of CD56+ natural killer cells. The CTLs directly contacted with neurons, as the authors showed previously for CD3+ and CD8+ T cells. CTLs were rare or absent in HIV nonencephalitis (HIVnE) and controls. Granzyme B and H precursor gene expression was up-regulated and interleukin (IL)-12A precursor, a maturation factor for natural killer cells and CTLs, was down-regulated in HIVE versus HIVnE brain. This study demonstrates, for the first time, CTLs in HIVE and shows that parenchymal T cells and CTLs are sensitive biomarkers for HIVE. Consequently, CD8+ T cells and CTLs could mediate brain injury in HIVE and may represent an important biomarker for productive brain infection by HIV-1.