title: New tools to expand regulatory T cells from HIV-1-infected individuals.
abstract: CD4+ Regulatory T cells (Tregs) are potent immune modulators and serve an important function in human immune homeostasis. Depletion of Tregs has led to measurable increases in antigen-specific T cell responses in vaccine settings for cancer and infectious pathogens. However, their role in HIV-1 immuno-pathogenesis remains controversial, as they could either serve to suppress deleterious HIV-1-associated immune activation and thus slow HIV-1 disease progression or alternatively suppress HIV-1-specific immunity and thereby promote virus spread. Understanding and modulating Treg function in the context of HIV-1 could lead to potential new strategies for immunotherapy or HIV vaccines. However, important open questions remain on their role in the context of HIV-1 infection, which needs to be carefully studied. Representing roughly 5% of human CD4+ T cells in the peripheral blood, studying the Treg population has proven to be difficult, especially in HIV-1 infected individuals where HIV-1-associated CD4 T cell and with that Treg depletion occurs. The characterization of regulatory T cells in individuals with advanced HIV-1 disease or tissue samples, for which only very small biological samples can be obtained, is therefore extremely challenging. We propose a technical solution to overcome these limitations using isolation and expansion of Tregs from HIV-1-positive individuals. Here we describe an easy and robust method to successfully expand Tregs isolated from HIV-1-infected individuals in vitro. Flow-sorted CD3(+)CD4(+)CD25(+)CD127(low) Tregs were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of IL-2. The expanded Tregs expressed high levels of FOXP3, CTLA4 and HELIOS compared to conventional T cells and were shown to be highly suppressive. Easier access to large numbers of Tregs will allow researchers to address important questions concerning their role in HIV-1 immunopathogenesis. We believe answering these questions may provide useful insight for the development of an effective HIV-1 vaccine.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, USA.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Angin
authors.forename: Melanie
authors.initials: M
authors.lastname: King
authors.forename: Marylyn Martina
authors.initials: MM
authors.lastname: Addo
mesh_terms: D003584:Cytological Techniques / Q000379:methods*; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology