Unique monocyte subset in patients with AIDS dementia

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

“…17,19,25,72 Peripheral correlates of SIVE underline the important concept that the mechanisms that drive neuropathogenesis are not limited to factors within the CNS compartment only. Notably, the range of values for plasma sCD163 and CD14 þ CD16 þ monocyte counts is greater between SIVE animals than between SIVnoE animals, suggesting that the animals that develop SIVE may have lost the ability to regulate monocyte homeostasis.…”

Macrophage/Microglial Accumulation and Proliferating Cell Nuclear Antigen Expression in the Central Nervous System in Human Immunodeficiency Virus Encephalopathy

“…16 In addition, monocytic cells within the nodular lesions and multinucleated giant cells are CD14ϩ/CD45(LCA)ϩ and CD16ϩ/HIV-1 p24ϩ. 16 The prominent CD16 expression on these perivascular macrophages is evidence for immunophenotypic similarity with circulating MPs in HIVD, supporting the hypothesis put forth by Pulliam and colleagues, 18 that an increased proportion of circulating monocytes in individuals with HIVD leads to CNS invasion and contributes to the pathogenesis of HIV-1 in the CNS. The immunophenotype of the perivascular MPs in HIVE, therefore, shows phenotypic similarity with that of MPs expanded in the peripheral blood in HIV/AIDS and even more so in the setting of HIVD.…”

“…The number of CD14ϩ/CD16ϩ cells has been demonstrated to be increased in circulation as well as in CNS tissue. If these activated MPs are indeed more invasive as has been suggested, 18 the detection of high levels in both circulating and CNS compartments might suggest an increase in the generation kinetics of these cells, or an increase in survival time, possibly even recirculation of tissue MPs back into the circulation. Interestingly, bone marrow from patients with HIV-1 infection and AIDS has been reported to contain a statistically significant increase in PCNAϩ macrophages, when compared to normal marrow, but these cells did not express detectable levels of topoisomerase II␣, a marker for DNA rep- The total number of PCNAϩ cells was significantly increased in HIVE relative to seronegative controls using the Tukey-Kramer test for multiple comparisons (P ϭ 0.048).…”

Neuropsychiatric Manifestations of HIV Infection and AIDS

“…There is some evidence that, despite the poor CNS penetration of most antiretrovirals, effective antiretroviral therapy may attenuate the neurotoxicity of circulating monocytes/macrophages. Among individuals with ADC receiving effective antiretroviral regimens, macrophage-derived soluble factors were found to be less neurotoxic than observed prior to the availability of combination antiretroviral therapy (Pulliam et al, 1997). The major difference between "HIV associated dementia complex" and "HIV associated minor cognitive/ motor disorder" is the severity of impairment in activities of daily living.…”

“…A particular subtype of monocyte/macrophages derived from the peripheral blood was found to be greatly increased among patients with AIDS dementia compared with both HIV infected and uninfected controls. Soluble factors from these macrophages were found to be highly neurotoxic--that is, they killed human brain cells in culture (Pulliam et al, 1997). Although the incidence of nearly all nervous system opportunistic infections has declined dramatically in the era of potent antiretroviral therapy, the impact on the incidence and prevalence of HIV-associated cognitive impairment including frank ADC--has been low.…”