Aberrant Induction of Regulatory Activity of CD4+CD25+ T Cells by Dendritic Cells in HIV-Infected Persons With Amebic Liver Abscess

To know why HIV-1-infected persons are particularly susceptible to amebic liver abscess (ALA), we investigated the role of CD4 + CD25 + T cells in the susceptibility of HIV-1-infected persons to this disease. Herein we show, in early stage HIV-1-infected subjects, that CD4 + T-cell responses to Entamoeba histolytica antigen (EhAg) were selectively impaired, especially in those with ALA. EhAg-specific CD4 + T-cell responses were normalized by depletion of CD4 + CD25 + cells or by addition of anti-cytotoxic T lymphocyte antigen 4 (CTLA4) antibody. Regulatory activity of CD4 + CD25 + T cells to suppress the EhAg-specific CD4 + T-cell response could be induced by EhAg-primed dendritic cells (DCs) in HIV-1-infected subjects, especially in those with ALA, but not in healthy controls. Exogenous Tat-incubated DCs derived from HIV-negative subjects also could upregulate CTLA4 expression on autologous CD4 + CD25 + T cells and selectively suppress the EhAg-specific CD4 + T-cell response. The results imply an interaction of the two pathogens: HIV-1, perhaps through the effect of Tat on DCs, may upregulate EhAg-specific regulatory T-cell activity to suppress T-cell response to E. histolytica, thus increasing the susceptibility to invasive amebiasis in even early-stage HIV-1-infected persons.