Background:  Opportunistic infections in the central nervous system (CNS) are responsible for the high mortality in patients with AIDS in developing countries. Inflammation triggered by opportunistic infections in the CNS lead to an increase of HIV burden and trafficking of infected cells into the brain. The immune mechanisms that regulate CNS brain inflammation may influence HIV replication and viral load in the CNS compartment. We studied the magnitude and profile of regulatory T cells (Treg) responses and HIV viral load in the cerebrospinal fluid (CSF) of patients with neuroAIDS-associated opportunistic infections to determine their role in immunopathogenesis.

Methods:  CSF and blood samples were obtained from patients with neuroAIDS at the Universidad del Valle University Hospital in Cali, Colombia. We determined the presence of Treg (CD3⁺CD4⁺CD25⁺FoxP3⁺; Treg) by flow cytometry analysis in CSF and peripheral blood mononuclear cells in 45 patients with well characterized neurological opportunistic infections (toxoplasma encephalitis [TE], cryptococcal meningitis [CM], and tuberculous meningitis [TBM]) and 11 HIV-infected controls without opportunistic infections. We quantified the HIV-1 viral load in paired CSF/plasma samples. Log₁₀ viral load and mean frequency of Treg (expressed as percentage of CD4 T cells) of patients with and without opportunistic infections of the CNS were compared (significance p ≤0.05).

Results:  Mean CSF viral load was higher in the opportunistic infections group as compared with controls (5.0 log vs 2.9 log; p = 0.002). Furthermore, CSF viral load distinguished CM or TBM from TE. Patients with meningitis had more viral copies in the CSF than toxoplasmic encephalitis (5.6 log vs 4.4 log; p = 0.013). Similarly, patients with opportunistic infections had higher percentages of CSF Treg cells (18.4% vs 5.8%; p = 0.033) and elevated Treg:  activated T cell ratio (0.31 vs 0.08; p = 0.005) as compared with controls without opportunistic infections. The mean percentage of Treg in the CSF of patients with opportunistic infection was markedly higher than in blood (p = 0.001). Similarly, the expression level of FoxP3 molecule in Treg (p <0.001) was higher in CSF, findings that indicate accumulation of suppressive T cell subset in the CNS compartment. In contrast to CSF, no differences were found in HIV-1 viral load, Treg cells or CD4 T cell counts in the blood.

Conclusions:  The increased accumulation of Treg cells and HIV load in the CSF of patients with neuroAIDS opportunistic infection supports the view that Treg cells contribute to an immune suppressive environment that facilitates HIV replication within the CNS.