2. Academic Validation
  3. Targeting CD8+ T cells in cardiovascular diseases: current options and therapeutic perspectives

Targeting CD8+ T cells in cardiovascular diseases: current options and therapeutic perspectives

  • Cardiovasc Res. 2025 Oct 24;121(12):1830-1842. doi: 10.1093/cvr/cvaf098.
Rida Al-Rifai 1 2,  Vincent Duval 1 2,  Icia Santos-Zas 3,  Théo Guyon 1 2,  Luna Chetrit 1 2,  Corinne Tanchot 1,  Clement Cochain 1 4,  Alma Zernecke 4,  Marc Vocanson 5,  Benoit Bensaid 6,  Alain Tedgui 1,  Heinz-Peter Schultheiss 7,  Christian Baumeier 7,  Christian Bailly 8,  Hafid Ait-Oufella 1 2 9
Affiliations

Affiliations

  • 1 Université Paris Cité, INSERM U970, Paris Cardiovascular Research Center, 56 Rue Leblanc, 75015 Paris, France.
  • 2 POLYGON Therapeutics, 56 Rue Leblanc, 75015 Paris, France.
  • 3 Laboratorio de Endocrinología Celular, Área de Endocrinología Molecular y Cellular Instituto de Investigación Sanitaria de Santiago, Complejo Hospitalario Universitario de Santiago (CHUS), Hospital Clínico Universitario de Santiago, Choupana s/n, 15706 Santiago de Compostela, Spain.
  • 4 Institute of Experimental Biomedicine, University Hospital Würzburg, Germany.
  • 5 Centre International de Recherche en Infectiologie (CIRI), Centre National de la Recherche Scientifique, INSERM U1111, Unité Mixte de Recherche 5308, Ecole Normale Supérieure de Lyon, Lyon, France.
  • 6 Drug Allergy Reference Center, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Dermatologie, Lyon, France.
  • 7 Institute of Cardiac Diagnostics and Therapy, IKDT GmbH Berlin 12203, Germany.
  • 8 Centre International de Recherche en Infectiologie - INSERM U1111, 21 Avenue Tony Garnier, 69007 Lille, France.
  • 9 Service de Médecine Intensive-Réanimation, Assistance Publique, Sorbonne Université, Hôpitaux de Paris, Paris, France.
PMID: 40448685 DOI: 10.1093/cvr/cvaf098
Abstract

T lymphocytes expressing the CD8 coreceptor, often referred to as cytotoxic T lymphocytes, are critical in defending against virus infections and cancers. CD8 encompasses a diverse family of proteins, including homodimers, heterodimers, isoforms, and splice variants. CD8αβ heterodimers are the predominant form of the CD8 membrane protein, often anchored to lipid rafts to facilitate the activation of the T cell receptor. Small molecules like itaconate have been shown to modulate CD8+ T cell expression. Anti-CD8 monoclonal antibodies (mAbs) targeting either CD8α or CD8β are available to study the functions of CD8+ cells in experimental models. Additionally, various immuno-imaging probes, such as 89Zr-crefmirlimab berdoxam, have been developed to predict the response of cancers to immunotherapy. The potential use of anti-CD8 mAbs to treat diseases associated with hyperactivation of cytotoxic CD8+ T cells is also under investigation. This includes conditions such as acute (e.g. ischaemic heart failure, ischaemic stroke), subacute (e.g. myocarditis), and chronic cardiovascular diseases (atherosclerosis). The use of anti-CD8 mAbs represents a promising therapeutic strategy to combat diseases characterized by excessive cytolytic activity of T cells. Experimental models have shown that anti-CD8 depleting mAbs can effectively limit tissue damages caused by CD8+ T cells. As a result, the time is ripe to evaluate these treatments in humans. Preclinical development of the first therapeutic anti-CD8 mAb (PLG101) is currently underway.

Keywords

CD8; Cardiovascular; Cytotoxicity; Inflammation; Lymphocyte.

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