Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection.

Background: CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3 CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3 CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known.

Methods: Pleural fluid mononuclear cells (PFMC) from HIV/TB co-infected patients with pleural TB were characterized by immune-staining and FACS analysis for surface markers CD4, CD127, CCR5, CXCR4, HLA-DR and intracellular expression of Foxp3, HIVp24, IFN-γ and Bcl-2. Whole PFMC and bead separated CD4CD25CD127 T cells were assessed for HIV-1 LTR strong stop (SS) DNA by real-time PCR, which represents viral DNA post cell entry and initiation of reverse transcription.

Results: High numbers of HIV-1 p24 positive Foxp3 and Foxp3CD127 CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4Foxp3CD127 T cells displayed high expression of the cellular activation marker, HLA-DR. Further, expression of the HIV-1 co-receptors, CCR5 and CXCR4, were higher on CD4Foxp3T cells compared to CD4Foxp3 T cells. Purified CD4CD25CD127 T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4Foxp3T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4CD25CD127 T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24 Foxp3 CD4T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24 Foxp3 CD4 T cells, and Foxp3 CD4T cells without HIV-p24 expression.

Conclusion: Foxp3 CD4 T cells in PFMC from HIV/TB co-infected subjects are predisposed to productive HIV-1 infection and have survival advantage as compared to Foxp3 negative CD4 T cells.