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HIV-producing T cells in cerebrospinal fluid
Jutta K Neuenburg1, Elizabeth Sinclair, Annelie Nilsson
1Gladstone Institute of Virology and Immunology, San Francisco, CA, USA.
Insights
In HIV-1 infection, HIV-1-producing T cells are found in cerebrospinal fluid (CSF). Their numbers correlate with viral load in CSF, though white cell counts are better predictors.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Cerebrospinal fluid (CSF) white cell count correlates with HIV-1 viral load.
- The presence and role of HIV-1-producing T cells in CSF are not fully understood.
Purpose of the Study:
- To determine if HIV-1-producing T cells are present in CSF.
- To assess the correlation between these cells and CSF viral load.
Main Methods:
- Developed a flow cytometry assay to detect intracellular p24 HIV-1 antigen in T cells.
- Analyzed T cell populations, including activated CD38+ CD4 T cells, in CSF.
Main Results:
- Most CSF T cells, including activated ones, were not HIV-1 producing.
- The fraction of activated CD38+ CD4 T cells in CSF was independently associated with HIV-1-producing T cells.
- Percentage and number of HIV-1-producing T cells correlated with CSF viral load.
Conclusions:
- HIV-1-producing T cells are present in the CSF.
- CSF white cell count remains the best predictor of CSF viral load, suggesting many uninfected cells.
- Systemic inflammation and immune activation may influence CSF white cell counts and viral load.
Abstract:
In HIV-1-infected subjects, the magnitude of HIV-1 viral load in cerebrospinal fluid (CSF) correlates with the CSF white cell count. To determine whether HIV-1-producing T cells appear in CSF and whether their percentage and number correlate with viral load in CSF, we developed a flow cytometric assay that detects HIV-1-producing T cells by identifying intracellular p24 HIV-1 antigen. We found that most CSF T cells were not HIV-1 producing, even when cell-free viral load in CSF was high. Most activated T cells in CSF were also not HIV-1 producing, but the activated CD38+ CD4 T-cell fraction in CSF was independently associated with the fraction of HIV-1-producing T cells in CSF. We conclude that HIV-1-producing T cells appear in CSF and that their percentage and number correlate with cell-free viral load in CSF, even though the CSF total white cell count remains the best predictor for CSF viral load. In HIV-1 infection, CSF white cell counts seem to contain a large number of uninfected cells. White cell counts and viral load in CSF may result from systemic inflammation and immune activation.
