title: Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection.
abstract: 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 CD4+CD25+CD127-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 Foxp3+CD127-CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4+Foxp3+CD127-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 CD4+Foxp3+T cells compared to CD4+Foxp3-T cells. Purified CD4+CD25+CD127-T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4+Foxp3+T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4+CD25+CD127-T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24+Foxp3+CD4+T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24+Foxp3-CD4 T cells, and Foxp3+CD4+T cells without HIV-p24 expression.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases, Case Western Reserve University, Cleveland OH.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hirsch
authors.affiliation: Joint Clinical Research Center, Kampala, Uganda.
authors.forename: Joy
authors.initials: J
authors.lastname: Baseke
authors.affiliation: Makerere University, Kampala, Uganda, National Tuberculosis and Leprosy Program, Kampala, Uganda.
authors.forename: John Lusiba
authors.initials: JL
authors.lastname: Kafuluma
authors.affiliation: Makerere University, Kampala, Uganda, National Tuberculosis and Leprosy Program, Kampala, Uganda.
authors.forename: Mary
authors.initials: M
authors.lastname: Nserko
authors.affiliation: Joint Clinical Research Center, Kampala, Uganda; Makerere University, Kampala, Uganda, National Tuberculosis and Leprosy Program, Kampala, Uganda.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Division of Infectious Diseases, Case Western Reserve University, Cleveland OH; Veterans Affairs Medical Center, Cleveland, OH.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
keywords: Apoptosis; Bcl-2; Foxp3; HIV-1 LTR; HIV-1 p24; HIV/TB co-infection; Pleural TB; Regulatory T-cell