CD8+CD28-CD127loCD39+Treg Expansion: a New Pathogenic Mechanism for HIV Infection?

HIV-associated immunodeficiency is related to loss of CD4+ T cells. This mechanism does not explain certain manifestations of HIV disease such as immunodeficiency events in patients with >500 CD4+ T cells/ml or occurrence of non-AIDS tumors. Hence, it is possible that other pathogenic mechanisms causing immunodeficiency may be at play during HIV infection. Little is known about the role of regulatory T CD4+ cells (Treg) in HIV immunodeficiency pathogenesis and studies on CD4+ Treg in HIV infected patients led to controversial results (1). Interestingly, similarities in composition and function of Treg subsets between tumors and HIV infection have been highlighted (2). The regulatory T cell compartment includes cells belonging to the CD8+ T cell lineage (3). Among the various CD8+ Treg subsets, a subgroup characterized by the CD8+CD28-CD127loCD39+ phenotype has been found to be highly concentrated within the tumor microenvironment (4). By polychromatic flow cytometry we show that HIVinfected patients have elevated circulating levels of functional CD8+CD28-CD127lowCD39+ T regulatory cells. These cells have antigen specificity against HIV proteins, suggesting their origin from HIV-specific T lymphocytes. Their frequency post ǀ anti-retroviral therapy (ART) correlates with HIV viremia, CD4+ T cell count and immune activation markers, suggesting their pathogenic involvement in AIDS- or non-AIDS related complications. Their increase after initiation of ART heralds a lack of virological or clinical response: hence their monitoring is clinically relevant.