isolation-tonsillar-mononuclear-cells-to-study-ex-vivo-innate-immune

Isolation of Tonsillar Mononuclear Cells to Study Ex Vivo Innate Immune Responses in a Human Mucosal Lymphoid Tissue

Studying isolated cells from mucosa-associated lymphoid tissues (MALT) allows understanding of immune cells response in pathologies involving mucosal ...

Centre Interdisciplinaire Chimie Biologie

Université Paris Descartes

Université Paris Descartes, Sorbonne Paris Cité

Despite variability, the majority of HIV-1-infected individuals progress to AIDS characterized by high viral load and massive CD4+ T-cell depletion. However, there is a subset of HIV-1-positive individuals that does not progress and spontaneously maintains an undetectable viral load. This infrequent patient population is defined as HIV-1 controllers (HIV controllers), and represents less than 1% of HIV-1-infected patients. HIV-1-specific CD4+ T cells and the pool of central memory CD4+ T cells are also preserved despite immune activation due to HIV-1 infection. The majority of HIV controllers are also defined by the absence of massive CD4+ T-cell depletion, even after 10 years of infection. However, the mechanisms involved in protection against HIV-1 disease progression have not been elucidated yet. Controllers represent a heterogeneous population; we describe in this paper some common characteristics concerning innate immune response and CD4+ T cells of HIV controllers.

Characteristics of plasmacytoid dendritic cell and CD4+ T cell in HIV elite controllers.

TNF-related apoptosis ligand (TRAIL) induces apoptosis of HIV-1-exposed CD4 T cells expressing the death receptor 5 (DR5) in vitro and has been associated with reduced CD4 T cell number in viremic HIV-1-infected patients. Alterations of the TRAIL/DR5 apoptotic pathway could be involved in the absence of massive CD4 T cell depletion in HIV-1-infected controllers (HIC). We studied here apoptosis of CD4 T cells from HIV-infected progressors and controllers. Reduced apoptosis of CD4 T cells from HIC was observed upon HIV stimulation. This lower apoptosis correlated with a deficiency of DR5 cell surface expression by CD4 T cells upon HIV-1 stimulation. The significant lower apoptosis observed in CD4 T cells after HIV exposure, associated with lower expression of membrane DR5 could explain the better survival of HIV-specific CD4 T cells from HIV controllers. The levels of DR5 cell surface expression on CD4 T cells could represent a new prognostic marker. 

Jean-Philippe Herbeuval

CNRS UMR-8601

Centre Interdisciplinaire Chimie Biologie

Isolation of Tonsillar Mononuclear Cells to Study Ex Vivo Innate Immune Responses in a Human Mucosal Lymphoid Tissue

Jean-Philippe Herbeuval

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Centre Interdisciplinaire Chimie Biologie

Isolation of Tonsillar Mononuclear Cells to Study Ex Vivo Innate Immune Responses in a Human Mucosal Lymphoid Tissue

CNRS UMR-8601