Redistribution of FOXP3-positive regulatory T cells from lymphoid tissues to peripheral blood in HIV-infected patients.

OBJECTIVE: Regulatory T (Treg) cells are altered during HIV replication, but their role in chronic infection is controversial and lacks reproducibility between series. FOXP3 is a specific marker of Treg cells. We study for the first time FOXP3 expression in a unique series of paired samples at different time points of HIV infection.
DESIGN: Paired samples from lymphoid tissue and peripheral blood were simultaneously obtained from 27 HIV-infected patients (before and after highly active antiretroviral therapy [HAART]) and 6 controls.
METHODS: We analyzed FOXP3 expression by TaqMan (Universal PCR Master Mix; Applied Biosystems, Foster City, CA) reverse transcriptase polymerase chain reaction in lymphoid tissue and peripheral blood. Treg cells were assessed in lymphoid tissue by immunohistochemistry/computer image analysis and in peripheral blood by flow cytometry. CD4 cell counts and viral loads were obtained.
RESULTS: HIV-infected patients had a low FOXP3 copy number and Treg cell frequencies in lymphoid tissue but a high number of Treg cells in peripheral blood. Lymphoid tissue FOXP3 expression decreased after HAART, and it correlated to lymphoid tissue viral load. Patients treated with nonnucleoside HAART had the lowest lymphoid tissue FOXP3 expression.
CONCLUSIONS: HIV-infected patients had low FOXP3 expression in lymphoid tissue and redistributed Treg to peripheral blood. HAART reduced even more the proportion of lymphoid tissue Treg in association with the immunologic recovery observed after treatment. The type of HAART may have an impact on the distribution of Treg cells.