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

Tayma Shaaban Kabakibo; Edwige Arnold; Kartika Padhan; Audrée Lemieux; Gloria Gabrielle Ortega-Delgado; Jean-Pierre Routy; Naglaa Shoukry; Mathieu Dubé; Daniel E Kaufmann

doi:10.1016/j.isci.2024.110947

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

iScience. 2024 Sep 13;27(10):110947. doi: 10.1016/j.isci.2024.110947. eCollection 2024 Oct 18.

Authors

Tayma Shaaban Kabakibo^{1

2

3}, Edwige Arnold^{1

2}, Kartika Padhan¹, Audrée Lemieux^{1

2

3}, Gloria Gabrielle Ortega-Delgado¹, Jean-Pierre Routy^{4

5}, Naglaa Shoukry^{1

2

6}, Mathieu Dubé¹, Daniel E Kaufmann^{1

2

6

7}

Affiliations

¹ Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
² Université de Montréal, Montréal, QC, Canada.
³ Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.
⁴ Chronic Viral Illnesses Service and Division of Hematology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
⁵ Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada.
⁶ Département de Médecine, Université de Montréal, Montréal, QC H2X 0A9, Canada.
⁷ Division of Infectious Diseases, Department of Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.

Abstract

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.

Keywords: Immunology; Virology.