Changes in helper lymphocyte chemokine receptor expression and elevation of IP‐10 during acute respiratory syncytial virus infection in infants

Abstract

It is known that lymphopenia caused by apoptosis may occur during severe respiratory syncytial virus (RSV) infection. However, further evidence about how T-cell subsets may be affected in infants during severe RSV bronchiolitis is needed to understand the mechanisms through which immunological memory may be altered. There is increasingly convincing evidence that RSV may be associated with the development of atopy and asthma. Surrogates of Th1, Th2 and regulatory T-lymphocyte populations were measured in blood from children with acute RSV bronchiolitis and in convalescence using the cell surface receptors CXCR3, CCR4 and CD25, respectively. Samples were also obtained from healthy age-matched controls. Plasma levels of the chemokines interferon-γ inducible protein-10 (IP-10) and thymus and activation-regulated chemokine (TARC), which are known ligands for CXCR3 and CCR4, were also measured. Free plasma DNA was measured using quantitative PCR. CXCR3-positive cells were significantly decreased during acute infection (p = 0.013), while CCR4 and CD25 T-cell populations were unchanged. Plasma levels of IP-10 were markedly elevated in acute infection (p = 0.001). Convalescent samples were not significantly different to control samples for lymphocyte phenotypes or plasma chemokines. Elevated free plasma DNA was detected during acute infection compared with convalescence and controls. A profound reduction in the Th1, but not Th2, and CD25-positive lymphocyte populations associated with exaggerated IP-10 production occurs in severe RSV bronchiolitis. Free DNA is detectable in plasma. This may allow significant alterations in the generation of T-cell memory.

Airway CD8+T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

“…The overall functional capacities of human infant T cells as being skewed toward Th2 or antiinflammatory responses (8) is largely derived from studies of umbilical cord blood (24)(25)(26). Measuring the in vivo infant immune response to VRTI has been more challenging, and has involved characterization of cells and cytokines in peripheral blood (6,21,27,28), nasopharyngeal washes (29,30), or tracheal aspirates (31,32). However, sampling remains limited, and unifying immune parameters related to disease outcome and severity has not emerged.…”

Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4

“…35,36 Mast cells are a major source of mediators associated with bronchoconstriction, such as leukotriene C 4 (LTC 4 ), 18 and can also produce other mediators found to be increased in the sputum and lavage fluid of patients with RSV infections. 15,18,32,[37][38][39] These findings suggest that mast cell responses to RSV can contribute to the pathogenesis of the disease.…”

Mucosal IgG Levels Correlate Better with Respiratory Syncytial Virus Load and Inflammation than Plasma IgG Levels

“…This shows that mucosal IgG levels are a better correlate than plasma IgG levels for viral load. High CXCL10 plasma levels are indicative of RSV-associated inflammation (14). Therefore, we tested whether mucosal and plasma CXCL10 levels correlated with RSV load.…”