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Unique monocyte subset in patients with AIDS dementia
L Pulliam1, R Gascon, M Stubblebine
1Department of Laboratory Medicine, University of California, San Francisco, USA. pulliam@pangloss.ucsf.edu
Background:
15-30% of patients infected with HIV will develop a debilitating dementia. Whilst HIV enters the brain soon after infection, presumably within monocyte-derived macrophages, not all patients with HIV become demented. Blood monocytes probably cross the blood-brain barrier and give rise ultimately to parenchyma macrophages. We looked for a specific monocyte subset in AIDS patients with dementia.
Methods:
Peripheral blood monocytes from three groups were compared: AIDS patients with (n = 12) and without (n = 11) dementia, and ten HIV seronegative healthy controls. We used flow cytometry to analyse monocytes, and cell lysis and apoptosis assays to examine monocyte effects on human brain cells in vitro.
Findings:
We found a unique subset of monocytes in patients with AIDS dementia. These monocytes were more dense and granular and expressed CD14/CD16 and CD14/CD69. Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients). The corresponding means for CD14/CD69 were 7% (6), 8% (10), and 69% (18) (p < 0.0001).
Interpretation:
CD69 is a member of the natural-killer-cell gene complex that is expressed after activation. Supernatants from cultures containing these dense cells can trigger apoptosis of human brain cells in vitro. The monocyte subset we found in patients with AIDS dementia might enter the brain and expose neural cells to toxic factors.
Insights
A unique monocyte subset, expressing CD14/CD16 and CD14/CD69, was identified in HIV-infected patients with dementia. These cells may contribute to neurodegeneration by inducing apoptosis in brain cells.
Area of Science:
- Neuroimmunology
- Virology
- Cell Biology
Background:
- 15-30% of individuals with HIV develop dementia.
- HIV enters the brain via monocyte-derived macrophages, but not all infected individuals develop dementia.
- Blood monocytes are implicated in crossing the blood-brain barrier to form brain macrophages.
Purpose of the Study:
- To identify specific monocyte subsets associated with dementia in patients with Acquired Immunodeficiency Syndrome (AIDS).
Main Methods:
- Peripheral blood monocytes were analyzed from three groups: AIDS patients with dementia (n=12), AIDS patients without dementia (n=11), and HIV-negative controls (n=10).
- Flow cytometry was used to analyze monocyte subsets.
- Cell lysis and apoptosis assays examined monocyte effects on human brain cells in vitro.
Main Results:
- A distinct monocyte subset was found in AIDS dementia patients, characterized by increased density, granularity, and expression of CD14/CD16 and CD14/CD69.
- Mean CD14/CD16 expression was significantly higher in AIDS dementia patients (37%) compared to non-dementia AIDS patients (16%) and controls (6.5%).
- Mean CD14/CD69 expression was markedly elevated in AIDS dementia patients (69%) versus non-dementia AIDS patients (8%) and controls (7%).
Conclusions:
- CD69, a marker of cell activation, was highly expressed on the identified monocyte subset.
- Supernatants from these dense monocytes induced apoptosis in human brain cells in vitro.
- This specific monocyte subset may infiltrate the brain and release factors toxic to neural cells, contributing to AIDS dementia.