Author(s): Suchard MS, Mayne E, Green VA, Shalekoff S, Donninger SL, , Suchard MS, Mayne E, Green VA, Shalekoff S, Donninger SL,
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Abstract BACKGROUND: Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations 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 HIV-infected individuals and uninfected controls together with expression of CD25, GITR and CTLA-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\%-26.27\%) than healthy controls (median 3.72\%; range 1.3-7.5\%; P = 0.002), despite having lower absolute 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 negative correlation with CD4 count (rho = -0.423 P = 0.044). 48\% of our patients had CD4 counts below 200 cells/microl 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 high FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by individual 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.
This article was published in PLoS One
and referenced in Journal of AIDS & Clinical Research