Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis

Renzi, Paolo; Turgeon, Julie; Yang, Jian; Drblik, Susan Pamela; Marcotte, Jacques-Édouard; Pedneault, Louise; Spier, Sheldon

doi:10.1016/s0022-3476(97)70243-9

Cited by 91 publications

(71 citation statements)

References 40 publications

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“…In addition, infants are prone to generate type 2 T-cell responses in the first few months of life, presumably because of the Th2 cytokine-enriched environment in utero (25). Type 2 T-cell responses have been observed in infants with LRT disease caused by RSV (3,(42)(43)(44). Elevated serum IgE levels and peripheral blood eosinophilia at the time of RSV infection have been further associated with asthma (56).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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It is essential that preventative vaccines for respiratory syncytial virus (RSV) elicit balanced T-cell responses. Immune responses dominated by type 2 T cells against RSV antigens are believed to cause exaggerated respiratory tract disease and may also contribute to unwanted inflammation in the airways that predisposes infants to wheeze through adolescence. Here we report on the construction and characterization of recombinant RSV (rRSV) strains with amino acids 151 to 221 or 178 to 219 of the attachment (G) glycoprotein deleted (rA2cp⌬G150-222 or rA2cp⌬G177-220, respectively). The central ectodomain was chosen for modification because a peptide spanning amino acids 149 to 200 of G protein has recently been shown to prime several strains of naïve inbred mice for polarized type 2 T-cell responses, and peripheral blood T cells from most human donors recognize epitopes within this region. Quantitative PCR demonstrated that synthesis of nascent rRSV genomes in human lung epithelial cell lines was similar to that for the parent virus (cp-RSV). Plaque assays further indicated that rRSV replication was not sensitive to 37°C, but pinpoint morphology was observed at 39°C. Both rRSV strains replicated in the respiratory tracts of BALB/c mice and elicited serum neutralization and anti-F-protein immunoglobulin G titers that were equivalent to those elicited by cp-RSV and contributed to a 3.9-log 10 -unit reduction in RSV A2 levels 4 days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either rA2cp⌬G150-222 or rA2cp⌬G177-220. These findings are important for the development of attenuated RSV vaccines.

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Section: Discussionmentioning

confidence: 99%

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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“…With respect to the infection component in the scheme, the relevant recent observations are as follows: 1) genetic risk for atopy has been reported to be associated with increased susceptibility to severe RSV infection and bronchiolitis [61]; atopy in children has also been linked to increased susceptibility to measles-mumps-rubella [62] as well as to frequent upper respiratory tract infections [63]; 2) IFN-c responses in peripheral blood mononuclear cells are attenuated during acute RSV infection in children who develop bronchiolitis [59][60][61][62][63][64][65][66][67][68][69], suggesting that downregulated Th1 function may be associated with pathogenesis; 3) susceptibility to development of acute RSV bronchiolitis during infancy is associated with decreased levels of IL-12 in cord blood relative to subjects who do not develop bronchiolitis [70], suggesting a pre-existing deficiency in Th1 function in this group; 4) nonatopic wheezing children, in whom the principal stimulus for wheeze is viral infection per se, also have manifest reduced IFN-c responses [71]; and 5) a recent study by the authors9 group on a prospective cohort of infants followed to 18 months indicated that the development of T-cell memory to RSV (as a surrogate marker for RSV infection) during the observation period was inversely related to kinetics of postnatal maturation of IFN-c responses [72].…”

Section: The Apparent Dualistic Effects Of Respiratory Tract Infectiomentioning

confidence: 99%

Interactions between respiratory tract infections and atopy in the aetiology of asthma

Holt

Sly²

2002

European Respiratory Journal

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The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context.The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy.Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli. It is evident from a wide range of studies carried out in different geographical areas, that the prevalence of allergic diseases, and in particular atopic asthma, has increased markedly over the last 2-3 decades. Moreover, the increases become evident in successive birth cohorts during early childhood. It is also generally accepted that "diagnostic shift" is not a significant factor in these changes. Accordingly, given the timeframe over which the changes have occurred, the responsible factor(s) must be environmental, presumably interacting with one or more susceptibility genes.The search for the relevant genetic and environmental factors continues, and a variety of potential candidates have been identified. Prominent amongst these are factors related to respiratory infections, particularly those occurring in childhood. Paradoxically, these infections have been invoked both as potential protective factors in relation to asthma/ allergy development, and as triggers of asthma exacerbations in atopic asthmatics. The mechanisms by which these effects may be mediated are incompletely understood; however, recent findings suggest some intriguing new possibilities, which are discussed in this review. T-cell immunity to inhalant allergens: the basis of variations in responder phenotype within the adult populationThe epithelial surface of the upper and lower respiratory tract are continuously exposed to an array of pathogenic and nonpathogenic airborne antigens, and the induction and local expression of local T-cell immunity must accordingly be tightly controlled, in order to avoid the pathological consequences of chronic T-cell-driven inflammation. While it is highly plausible that resistance to airborne pathogens is a direct function of the speed of mobilization and the intensity of expression of local innate and adaptive immune mechanisms in the lung, the conve...

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“…Seperti telah diketahui bersama IL-4 merupakan sitokin utama yang mengatur produksi IgE pada asma. Peningkatan produksi IL-4 memicu peningkatan kadar IgE melalui switching sel B ke sel plasma atau sel TCD4 + berdiferensiasi menjadi sel Th2 (11)(12)(13). Dalam penelitian ini terjadi peningkatan kadar IL-4 dan rasio IL-4 / IFN-γ yang bermakna pada penderita bronkiolitis akut RSV dimasa bayi dan berkembang menjadi asma pada usia 7 tahun.…”

Section: Diskusiunclassified

Prediktor Asma Pada Usia 7 Tahun Setelah Menderita Bronkiolitis Akut Karena Respiratory Syncytial Virus: Suatu Studi Prospektif

Kusuma

2013

JKB

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Infants are at increased risk of developing asthma after RSV (Respiratory Syncytial Virus) acute bronchiolitis. The hypothesis that cytokine production is related to the development of asthma after RSV bronchiolitis. The diagnosis of RSV bronchiolitis was verified using the Abbott test pack RSV, a rapid enzyme immuno assay for direct detection of viral antigen in nasopharyngeal secretion. Changes in FEV1 (Forced Expiratory Volume in 1 second) were determined using spirometri, IL-4 and IFN-γ levels were determined using the enzyme-linked immunosorbant assay (ELISA) method. In this study, 62 children hospitalized for RSV bronchiolitis were followed prospectively, 55 (88.7%) children completed the study and 41 children (74.5%) had asthma at 7 years of age. RSV bronchiolitis children were more frequent among boys (boy /girl ratio: 2). Episodes of wheezing more than 8 had specifity and sensitivity of 100% respectivelly, might be the very useful predictor for asthma. The cut off level over 40.84 pg/ml for IL-4, below 14.12 pg/ml for IFN-γ, IL-4 / IFN-γ ratio over 3 and episodes of wheezing over 8 may be used to predict asthma after RCV bronchiolitis. Infants with asthma had higher IL-4 levels (p = 0.004) lower levels of IFN-γ (p = 0.599), higer IL-4 / IFN-γ ratio (p = 0.000) and higer episodes of wheezing (p = 0.000) when compared with those who had no asthma. In conclusions, the higher levels of IL-4, higher IL-4 /IFN-γ ratio, lower IFN-γ levels at the time of RSV bronchiolitis and higher episodes of wheezing may be used to predict asthma after RSV bronchiolitis later in life.Key words: respiratory syncytial virus (RSV), bronchiolitis, asthma, IL-4, IFN-γ, IL-4 / IFN-γ ratio, wheezing episodes, FEV1. PENDAHULUANPenderita bronkiolitis akut yang dirawat inap mempunyai risiko tinggi untuk mengalami mengi berulang dan penurunan faal paru sampai usia 7 -11 tahun. Jika penyebab bronkiolitis adalah Respiratory Syncytial Virus (RSV) maka risiko untuk terjadinya serangan mengi berulang dan penurunan faal paru sampai usia 7 -11 tahun menjadi makin meningkat (1,2,3). Asosiasi epidemiologi antara bronkiolitis RSV dengan serangan mengi berulang dan asma dikemudian hari selalu menjadi perdebatan para ahli. Beberapa prediktor yang dapat menentukan terjadinya asma dikemudian hari antara lain: ibu atau ayahnya menderita asma, mempunyai saudara asma, serangan wheezing nya terjadi sebelum usia 2 tahun dan mengalami serangan sedikitnya 10 kali, sering mengalami infeksi saluran nafas bawah, bayi lahir prematur, bayi laki-laki, kemiskinan, ras kulit berwarna, tidak pernah mendapat ASI dan ibu perokok.Penelitian-penelitian untuk membuktikan adanya hubungan tersebut terutama difokuskan pada mekanisme imunologis terjadinya disregulasi pola sitokin. Ketidakseimbangan atau terjadinya pergeseran dari sel T-helper (Th) tipe 1 dan tipe 2 (Th1 dan Th2) dan pada respon sitokin yang diproduksi merupakan ranah penelitian yang banyak dilakukan baik terhadap penderita maupun pada model binatang percobaan (4). Walaupun demikian beberapa peneliti...

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Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis

Cited by 91 publications

References 40 publications

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Interactions between respiratory tract infections and atopy in the aetiology of asthma

Prediktor Asma Pada Usia 7 Tahun Setelah Menderita Bronkiolitis Akut Karena Respiratory Syncytial Virus: Suatu Studi Prospektif

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