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

Objective: 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: FoxP3CD8 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-DR, 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-DR and Ki-67. However, compared with FoxP3CD4 cells, FoxP3CD8 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-DR, Ki-67, and PD-1 compared with non-HIV donors and treated patients.

Conclusions: FoxP3CD8 T cells are phenotypically distinct from FoxP3CD4 and FoxP3CD8 T cells. Expression of FoxP3 is associated with cellular activation in both CD4 and CD8 T cells.