Porcine γδ T cells express cytotoxic cell-associated markers and display killing activity but are not selectively cytotoxic against PRRSV- or swIAV-infected macrophages

• Published in: Frontiers in immunology 2024-07, Vol.15, p.1434011
• Main Authors: Bettin, Leonie, Darbellay, Joseph, van Kessel, Jill, Dhar, Neeraj, Gerdts, Volker
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Cells, Cultured; cytotoxicity; Cytotoxicity, Immunologic; Immunology; Influenza A Virus; Intraepithelial Lymphocytes - immunology; Macrophages, Alveolar - immunology; Macrophages, Alveolar - virology; Orthomyxoviridae Infections - immunology; PAMs; Perforin - immunology; Perforin - metabolism; phenotype; Porcine Reproductive and Respiratory Syndrome - immunology; Porcine respiratory and reproductive syndrome virus - immunology; Porcine respiratory and reproductive syndrome virus - physiology; Porcine γδ T cells; PRRSV; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Swine; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1434011

Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions. In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells. Our results show that only CD2 γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms. Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ T cells recognize target cells are not fully understood but may involve the detection of cellular stress signals.