CD4+ and CD8+ T cells expressing FoxP3 in HIV-infected patients are phenotypically distinct and influenced by disease severity and antiretroviral therapy

Objectives: Forkhead box P3 (FoxP3) is critical for the development of CD4+ regulatory T (Treg) cells and is a useful marker to identify this population. Recently, expression of FoxP3 was reported in human CD8+ T cells from the blood of untreated HIV-infected individuals. We assessed whether FoxP3 expression in CD8+ T cells is associated with suppressive potential and/or with HIV-associated immune activation.Methods: FoxP3+CD8+ T cells in non-HIV donors and in untreated and treated HIV-infected patients were identified by flow cytometry, then examined for coexpression of other Treg cell-associated markers [cytotoxic T lymphocyte-associated antigen (CTLA)-4, GITR, and CD45RO], markers of activation [HLA-DRHI, Ki-67, and programmed death (PD)-1], and markers of senescence (CD57 without CD28).Results: Similar proportions of FoxP3-expressing CD4+ and CD8+ T cells coexpressed HLA-DRHI and Ki-67. However, compared with FoxP3+CD4+ cells, FoxP3+CD8+ cells expressed less CTLA-4, CD28, and CD45RO but more PD-1 and CD57. FoxP3-expressing CD4+ and CD8+ cells from untreated patients exhibited higher expression of HLA-DRHI, Ki-67, and PD-1 compared with non-HIV donors and treated patients.Conclusions: FoxP3+CD8+ T cells are phenotypically distinct from FoxP3+CD4+ and FoxP3-CD8+ T cells. Expression of FoxP3 is associated with cellular activation in both CD4+ and CD8+ T cells.