FOXP3 expression is upregulated in CD4+T cells in progressive HIV-1 infection and is a marker of disease severity

Abstract

Background: Understanding the role of different classes of T cells during HIV infection is ritical to determining which responses correlate with protective immunity. To date, it is unclear hether lterations in regulatory T cell (Treg) function are contributory to progression of HIV infection. Methodology: FOXP3 expression was measured by both qRT-PCR and by flow cytometry in IV-infected individuals and uninfected controls together with expression of CD25, GITR and TLA-4. Cultured peripheral blood mononuclear cells were stimulated with anti-CD3 and cell proliferation was assessed by CFSE dilution. Principal Findings: HIV infected individuals had significantly higher frequencies of CD4+FOXP3+ T cells (median of 8.11%; range 1.33%- 6.27%) than healthy controls (median 3.72%; range 1.3-7.5%; P = 0.002), despite having lower bsolute counts of CD4+FOXP3+ T cells. There was a significant positive correlation between the frequency of CD4+FOXP3+ T cells and viral load (rho = 0.593 P = 0.003) and a significant gative correlation with CD4 count (rho =20.423 P = 0.044). 48% of our patients had CD4 counts below 200 cells/ml and these patients showed a marked elevation of FOXP3 percentage median 10% range 4.07%-26.27%). Assessing the mechanism of increased FOXP3 frequency, we found that the high FOXP3 levels noted in HIV infected individuals dropped rapidly in unstimulated culture conditions but could be restimulated by T cell receptor stimulation. This suggests that the igh FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by ndividual CD4+ T cells following antigenic or other stimulation. Conclusions/Significance: FOXP3 expression in the CD4+ T cell population is a marker of severity of HIV infection and a potential prognostic marker of disease progression. © 2010 Suchard et al.