Respiratory syncytial virus infection suppresses IFN-γproduction ofγδT cells

Abstract

SUMMARYThe immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. gd T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-g and interleukin (IL)-4 by mitogen-stimulated gd T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. gd T cells from RSV-infected infants had a lower proportion of IFN-g -producing cells (median, 4.00%; range, 0.58-6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13-2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43-61.21%; P < 0·01, median, 0.00%; range, 0.00-0.00%; P < 0·05) in the acute phase. By contrast, differences in cytokine production by total CD3 + T cells did not differ significantly between patient groups. Thus, reduced IFN-g -production by gd T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-g -producing gd T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02-1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25-10.98%; P < 0·005). Cytokine production by gd T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.

Mast Cell-Induced Lung Injury in Mice Infected with H5N1 Influenza Virus

“…However, our data further showed that abundant IFN-␥ was released by H5N1-infected mast cells in vitro. It has been well documented that influenza virus induces high levels of IFN-␥ in the lungs of infected animals, which is believed to be produced mainly by T and NK cells (1,42). In the present study, we demonstrated that mast cells released a high level of IFN-␥ after H5N1 virus infection in vitro, and this is believed to be the first report that IFN-␥ can be produced by activated mast cells, in addition to T and NK cells, in H5N1 virus infection.…”

γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease

“…In response to various bacterial and viral infections, ␥␦ T cells can rapidly produce cytokines, such as IFN-␥, TNF-␣, and IL-17 (82,(102)(103)(104)(105). However, mechanisms by which these pathogens elicit cytokine responses in ␥␦ T cells are poorly understood.…”

Animal Pneumoviruses: Molecular Genetics and Pathogenesis

“…Teng, Whitehead, and colleagues (346,378) have demonstrated the attenuation of hRSV NS-1 and M2-2 or NS-1 and SII deletion mutants in the chimpanzee model of infection, although without specific reference to interferonrelated phenomena. Interestingly, hRSV is sensitive to inhibition by gamma interferon (11,20,39,99,276,365), and potential hRSV-mediated modulation pathways have been identified (6,17).…”