Artificial antigen-presenting cell system reveals CD28’s role in modulating T cell functions during human immunodeficiency virus infection

作者：Tayma Shaaban Kabakibo, Edwige Arnold, Kartika Padhan, Audrée Lemieux, Gloria Gabrielle Ortega-Delgado, Jean‐Pierre Routy, Naglaa H. Shoukry, Mathieu Dubé, Daniel E. Kaufmann · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.110947 · 被引用次数：5 · 研究领域：Immune Cell Function and Interaction、HIV Research and Treatment、T-cell and B-cell Immunology

T cell immune dysfunction is a prominent feature of chronic HIV infection. To evaluate non-specific dysfunction, a method involving both generic activation and T cell receptor (TCR) stimulation is necessary. We created a tunable artificial antigen-presenting cell (aAPC) system. This system consists of lipid bilayers on cytometry-compatible silica microbeads (5 μm). When only anti-CD3 is incorporated, T cell activation is limited. Introducing anti-CD28 agonists significantly elevates the cytokine expression and upregulation of activation-induced markers. CD28 co-stimulation modulates the response profile, preferentially promoting IL-2 expression relative to other cytokines. aAPCs-stimulated CD4 + and CD8 + T cells from untreated HIV-infected individuals exhibit altered effector functions and diminished CD28 dependence. These functions are skewed toward TNFα, IFNγ and CD107a, with reduced IL-2. Antiretroviral therapy partially normalizes this distorted profile in CD4 + T cells, but not in CD8 + T cells. Our findings show T cell intrinsic biases that may contribute to persistent systemic T cell dysfunction associated with HIV pathogenesis.