Respiratory Syncytial Virus (RSV) Infects CD4⁺ T Cells: Frequency of Circulating CD4⁺ RSV⁺ T Cells as a Marker of Disease Severity in Young Children

• Published in: The Journal of infectious diseases Vol. 215; no. 7; pp. 1049 - 1058
• Main Authors: Raiden, Silvina, Sananez, Inés, Remes-Lenicov, Federico, Pandolfi, Julieta, Romero, Cecilia, De Lillo, Leonardo, Ceballos, Ana, Geffner, Jorge, Arruvito, Lourdes
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.04.2017
• Subjects: Adult; Biomarkers - blood; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Line; Female; Fetal Blood - cytology; Flow Cytometry; Humans; Infant; Infant, Newborn; Interferon-gamma - immunology; Interleukin-2 - immunology; Major; Male; PATHOGENESIS AND HOST RESPONSE; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus, Human; CD4; viral infection; infants; interleukin 2; interferon γ; T cells; respiratory syncytial virus; markers of disease severity; bronchiolitis; CD4+ T cells
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jix070

Background. Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4⁺ T cells to RSV infection. Methods. CD4⁺ and CD8⁺ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4⁺ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria. Results. CD4⁺ and CD8⁺ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4⁺ T cells. Respiratory syncytial virus antigens were detected in circulating CD4⁺ and CD8⁺ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4⁺ RSV⁺ T cells positively correlated with disease severity. Conclusions. Respiratory syncytial virus infects CD4⁺ and CD8⁺ T cells and compromises T-cell function. The frequency of circulating CD4⁺ RSV⁺ T cells might represent a novel marker of severe infection.