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Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases

PreDicta ended on March 31st 2016

Past news 

PreDicta Final Consortium Meeting took place  in Athens March 21st and 22nd 2016          

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All PreDicta's Newsletter can be found here 

Towards serological tests for the identification of RV strains causing asthma exacerbations

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Professor Nikolaos Papadopoulos is head of the Allergy Department of the National and Kapodistrian University of Athens. He has extensive experience and publication record on virus-induced inflammation in allergy and asthma. He is the winner of the prestigious PhARF (Phadia Allergy Research Forum) award 2010 which is awarded each year to a young scientist who has made outstanding contributions to the field of allergy.
Tasks in the project
Professor Nikolaos Papadopoulos will coordinate PreDicta. He will also lead the cohort (WP1) and take part in epithelium experiments (WP3), virus-bacteria interactions (WP4), regulatory cell research (WP5), antibody evaluation (WP7) and RV DNAzyme evaluation (WP8)
Team members
The NKUA team includes Assoc. Professor Maria Tsolia, specialist in Pediatric Infectious Diseases, with extensive experience in bacteriology and infection epidemiology, Dr P Xepapadaki who will lead the cohort recruitment and Dr C Skevaki, who will lead the epithelium experiments.
Relevant publications

  1. Papadopoulos NG et al. Rhinoviruses infect the lower airways. J Infect Dis 2000; 181:1875-1884.
  2. Papadopoulos NG et al. Association of rhinovirus infection with increased disease severity in acute bronchiolitis. Am J Respir Crit Care Med 2002; 165:1285-1289.
  3. Papadopoulos NG et al. A defective type 1 response to rhinovirus in atopic asthma. Thorax 2002; 57:328-332
  4. Tsolia MN et al. Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections. Clin Infect Dis. 2004;39:681-6.
  5. Xatzipsalti Met al. Rhinovirus viremia in children with respiratory infections. Am J Respir Crit Care Med 2005; 172:1037-1040.
  6. Xepapadaki P et al. Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy. J Allergy Clin Immunol 2005; 116:299-304.
  7. Psarras S et al. Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses. J Allergy Clin Immunol 2006; 117:291-297.

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Sebastian L Johnston
Pr SL Johnston has 20 years experience of working on infections and the pathogenesis of exacerbations of airway diseases. His group has extensive experience of all the techniques required to successfully complete the work proposed, including developing the first successful mouse model of rhinovirus infection and rhinovirus induced asthma exacerbation, clinical studies of infection and asthma and of primary epithelial cell s cultures and innate immune responses.
Tasks in the project
Pr SL Johnston will lead WP2 (mouse models of repeated RV infection and allergen exposure) and WP3 (development of in vitro models of RV infection of bronchial epithelial cells and allergen exposure). The ICL team will also provide mouse and epithelial samples for assay of mediators of resolution (WP6) and design RV-specific DNAzymes and evaluate then in mice (WP8).
Team members
The IMPERIAL team also includes Drs Nathan Bartlett and Ross Walton, who are both highly experienced in working in the rhinovirus mouse model, as well as Dr Michael R Edwards, whose areas of expertise are epithelial cell biology and innate immunity.
Relevant publications

  1. Wark PAB et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 2005;201: 937-947.
  2. Johnston SL et al. The Effect of Telithromycin in Acute Exacerbations of Asthma. N Engl J Med 2006;354:1589-600.
  3. Contoli M et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nature Med 2006;12:1023-1026.
  4. Bartlett NW et al. Mouse models of rhinovirus-induced disease & exacerbation of allergic airway inflammation. Nature Med 2008 Feb;14(2):199-204. Epub 2008 Feb 3.
  5. Message SD et al.  Rhinovirus induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci USA 2008;105:13562-7.

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Rudolf Valenta
Pr Valenta has more than 20 years experience in the field of molecular allergen characterization. His group has been the first to demonstrate the usefulness of recombinant allergens for in vitro allergy diagnosis in 1991 and has developed the first allergen chips containing micro-arrayed allergen molecules for allergy diagnosis. The group has recently studied rhinovirus-derived coat proteins as potential vaccine candidates for allergy and rhinovirus infections.  
Tasks in the project
MUW will co-ordinate WP 7 which is dedicated to the development of diagnostics for rhinovirus infections. Diagnostic tests developed by MUW will be used to study the immune responses in the longitudinal cohorts (WP1). Recombinant viral antigens, allergens and their epitopes made by MUW will be used as model antigens in mouse models (WP2), epithelial models (WP3), to study virus-bacteria interactions (WP4) and immune regulation (WP5). In addition, these antigens are available to WP 6 (resolution of inflammation) and WP 8 (interventions).
Team members
Staff involved in PREDICTA includes Katarzyna Niespodziana, a PhD student with a solid background in the characterization of recombinant rhinovirus coat proteins.
Relevant publications

  1. Hiller R et al. Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002;16(3):414-416.
  2.  Edlmayr J et al. A combination vaccine for allergy and rhinovirus infections based on rhinovirus- derived surface protein VP1 and a non-allergenic peptide of the major timothy grass pollen allergen, Phl p 1. J Immunol 2009;182:6298-306.
  3. Schulmeister U et al. Cloning, expression, and mapping of allergenic determinants of alphaS1-casein, a major cow's milk allergen. J Immunol 2009;182(11):7019-7029.
  4. Constantin C et al. Micro-arrayed wheat seed and grass pollen allergens for component-resolved diagnosis. Allergy 2009;64(7):1030-1037.
  5. Valenta R et al. From allergen genes to allergy vaccines. Ann. Rev. Immunol. 2010, in press.

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Mübeccel Akdis
Dr. Mübeccel Akdis’ group has demonstrated essential molecular and cellular differences between healthy and allergic immune response and has developed novel cell purification techniques and novel techniques for the analysis of small quantities of material, which is suitable for birth cohort studies.
Tasks in the project
Mübeccel Akdis is the leader of WP5 that looks into effects of viral infections on T-cell regulation. Her team will also contribute to WP3 with evaluation of tight junction function and  WP4, measuring transcription factors related to virus-bacteria interactions
Team members
Key staff involved includes Pr Cezmi Akdis (expertise in Immunology/epithelial) and Dr Liam O’Mahony (expertise in immunology/dendritic cells).
Relevant publications

  1. Akdis M et al. Healthy or allergic immune response characterized by fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 2004; 199: 1567-1575.
  2. Oral HB et al.  Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26. Eur J Immunol. 2006;36:380-8.  
  3. Deniz G et al. J Immunol. 2008 15;180:850-7.
  4. Meiler F. et al. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J. Exp. Med. 2008;205:2887-98.
  5. Klunker S et al. Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells. J Exp Med 2009. (In press).

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Evangelos Andreakos
BRFAA is going to participate in PreDicta through an interdisciplinary group that have joined forces and technologies to elucidate mechanisms preventing resolution of inflammatory responses:
*Laboratory of Immunogenetics led by Dr E. Andreakos (5a):This laboratory aims at elucidating molecular and cellular processes controlling chronic inflammation and preventing or promoting resolution.
*Laboratory of Pharmacology-Pharmacotechnology led by Dr C. Tamvakopoulos (5b): This laboratory explores and develops new therapeutic approaches, investigates the mechanisms of pharmacological action and examines the effects and interactions of drugs on living organisms at the cellular, molecular and biochemical level.
*Laboratory of Molecular Biology led by Prof. D. Thanos (5c): This laboratory investigates basic molecular mechanisms of gene expression with emphasis on the epigenetic mechanisms controlling gene transcription and on the establishment of stochastic gene expression patterns in human cells.
Tasks in the project
WP2:     Role of type I and type III IFNs in repeated RV infection models (5a)
WP3:     Elucidation of basic molecular mechanisms controlling type I IFN expression in the     bronchial     epithelium (5c)
WP4:    Measure pro-resolving lipid mediators (5b)
WP6:     Mechanisms of resolution of inflammation (5a and 5b).
WP8:     Development of novel targeted carriers for in vivo drug delivery to bronchial epithelium (5a)
Team members
*Team 5a includes Dr P. Sideras (Immunology, respiratory pathology), Dr I. Galani  (Immunology, Mouse models, delivery technologies) and Dr O. Koltsida (MD, Immunology, mouse models, lung physiology, asthma/rhinitis).
*Team 5b includes Dr A.Siskos (Pharmacology, quantitative analysis of drugs in biological fluids LC-MS/MS operation).
*Team 5c includes Dr M. Merika (Molecular and epigenetic mechanisms of gene expression).
Relevant publications

  1. (5a) Xirakia C et al. Am J Respir Crit Care Med (Accepted)
  2. (5a) Andreakos E et al. Arthritis Rheum. 2009; 60(4):994-1005.
  3. (5a) Andreakos E et al. Proc Natl Acad Sci U S A. 2006; 103(39):14459-64
  4. (5b) Siskos AP et al. J Proteome Res. 2009;8(7):3487-96
  5. (5b) Sofianos ZD et al. J Mass Spectrom. 2008;43(10):1381-92.
  6. (5b) Tamvakopoulos C. et al. Mass Spectrom Rev. 2007;26(3):389-402.
  7. (5c) Nolis, I. et al. Proc Natl Acad Sci USA (December 2009 issue, in press)
  8. (5c) Apostolou E, Thanos D. Cell. 2008;134(1):85-96
  9. (5c) Agelopoulos M, Thanos D. EMBO J. 2006 Oct 18;25(20):4843-53

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Marek L Kowalski
The group led by Pr Marek L Kowalski is involved in several research projects including longitudinal observations of patients with asthma ( DARE study), collections of biological samples for virus infections  detection, in vitro culture of primary epithelial cells from nasal polyps, in vitro infections of nasal epithelial cells  with respiratory viruses ( PIV-3).
Tasks in the project
WP1     Recruitment of observational cohort of children with asthma and follow up. Collecting     biological materials (sera, PBMCs, nasal swabs)
WP3     Recruitment of adult patients. Primary bronchial epithelial cell culture and RV infection
WP4     Primary nasal epithelial cell culture and evaluation of effects of viral and bacterial infections
WP5     Provision of cells and mRNA for regulation studies. Provision of adult asthma biopsies
WP6      Provision of biological materials for resolvin/protectin analysis. Assessments of RV-induced 15-HETE/lipoxins generation in nasal epithelial cells.    
Team members
LODZ team include Pawel Gorski MD,PhD (Patophysiology of asthma), Anna Lewandowska-Polak MD,PhD (Epithelial cell pathophysiology), Malgorzata Brauncajs PhD (Bacteriology, virology),  Joanna Makowska MD,PhD  (Severe asthma, clinician), Anna Sobańska MD   (Pediatrician), Dariusz Nowak MD,PhD  (Airway inflammation), Janina Grzegorczyk PhD  (Immunology, flow cytometry).
Relevant publications

  1. Makowska JS et al.  BMC Pulm Med. 2009 Jun 1;9:27.
  2. Spyridaki IS et al. J Virol Methods. 2009 Mar;156(1-2):102-6.
  3. Makowska JS et al. Ann Allergy Asthma Immunol. 2008 Oct;101(4):402-6.
  4. Piotrowski WJ et al. Pol Arch Med Wewn. 2009 Oct;119(10):628-35.
  5. Stefanska J et al. Pulm Pharmacol Ther. 2009 Sep 25.

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Claus Bachert
Claus Bachert is Professor of Medicine in the Ear Nose and Throat department at the University of Ghent in Belgium. Professor Bachert’s research interests include clinical and experimental allergology and immunology of the upper airways. He is leading the GA2LEN sinusitis cohort study, coordinating 9 European centres.
Tasks in the project
Pr Bachert will lead WP4 in Predicta. His team will also participate in the cohort study (WP1), investigate the mechanisms of epithelial penetration (WP3) and study the impact of viruses and staphylococcal enterotoxins on T-cell signatures, on dendritic and T cells (WP5).
Team members
Key experts involved in PreDicta are Thibaut Van Zele MD, PhD ( Immunology, Remodelling), Wang Xiang Dong MD (Mucosal immunology, clinical studies), Olga Krysko PhD (Animal models) and Gabriele Holtappels (technician: Luminex, FACS).
Relevant publications

  1. Patou J et al. Staphylococcus aureus enterotoxin B, protein A and lipoteichoic acid stimulations in nasal polyps. J Allergy Clin Immunol. 2008;121:110-5.  
  2. Van Bruaene N et al. T cell regulation in chronic paranasal sinus disease. J Allergy Clin Immunol 2008; 121:1435-1441
  3. Zhang Nan et al. Different types of T effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 2008 Nov;122(5):961-8
  4. Bachert C et al. Important research questions in allergy and related diseases: Chronic rhinosinusitis and nasal polyposis: A GA2LEN paper. Allergy 2009; 64: 520 – 533
  5. Van Bruaene N et al. TGF-beta signaling and collagen disposition in chronic rhinosinusitis. J Allergy Clin Immunol 2009; 124: 253-259

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Harald Renz
Harald Renz MD (Allergy research) is head of UNIMAR’s department of Clinical Chemistry and Molecular Diagnostics. His research program concentrates on translational research from bench to bedside in the field of the pathogenesis of allergic responses. He was among the first to develop animal model systems for various allergic phenotypes including most recently chronic asthmatic responses with airway remodeling.
Tasks in the project
Harald Renz will lead WP8 for the development of a DNAzyme specific to human RV, analysis of antiviral effectiveness in vitro and in vivo, testing of DNAzymes for therapeutic potential in a murine RV  model of asthma. His team will also participates in WP2 for the investigation of the role of the lung epithelial barrier in the interplay between RV infection and asthma.
Team members
UNIMAR’s team include Leigh Marsh PhD (Research in lung diseases); Tanja Dicke PhD (Allergy research); Petra Ina Pfefferle PhD (allergy research: Project management).
Relevant publications

  1. Tachdjian R et al. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.J Exp Med. 2009;206:2191-204.
  2. Conrad ML et al.  Maternal TLR signaling is required for prenatal asthma protection by the non-pathogenic microbe Acinetobacter lwoffii F78. J Exp Med, in press
  3. Sly PD et al. Early identification of atopy in the prediction of persistent asthma in children. Lancet. 2008;372:1100-6.
  4. Sel S et alEffective prevention and therapy of experimental allergic asthma using a GATA-3-specific DNAzyme. J Allergy Clin Immunol. 2008;12:910-916.e5.
  5. Sel S et al. Immunomodulatory effects of viral TLR ligands on experimental asthma depend on the additive effects of IL-12 and IL-10. J Immunol. 2007;178:7805-13.

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Tytti Vuorinen
Tytti Vuorinen is head of the virus laboratory (Department of Virology) at the University of Turku. The Department Virology has had research focus on respiratory viral infections over 3 decades. During the last decade rhinovirus has been one of the main interests.
Tasks in the project
UTU’s Department of Virology participates in the viral diagnostics (WP7), and evaluation of viral presence in tissue samples (WP4 and WP5).
Team members
Key team members include Tuomas Jartti MD PhD (Pediatric allergist) and Prof Olli Ruuskanen MD PHD (Senior scientist/consultant, expertise in Pediatr. Infect. Diseases).
Relevant publications

  1. Jartti T, van den Hoogen B, Garofalo RP, Osterhaus ADME, O Ruuskanen. New human metapneumovirus and acute wheezing in children. Lancet 2002;360:1393-4.
  2. Jartti T, Lehtinen P, Vuorinen T, Österbacka R, van den Hoogen B, Osterhaus ADME, Ruuskanen O. Respiratory picornaviruses and respiratory syncytial virus are the major causative agents of acute expiratory wheezing in children. Emerg Infect Dis 2004;10:1095-101.
  3. Allander T, Jartti T, Gupta S, Niesters H, Lehtinen P, Österback R, Vuorinen T, Waris M, Tivejung-Lindell A, van den Hoogen B, Hyypiä T, Osterhaus A, Ruuskanen O. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904-10.
  4. Jartti T, Lee WM, Pappas T, Lemanske RF Jr, Gern JE. Serial viral infections in infants with recurrent respiratory illnesses Eur Respir J 2008;32:314-20.
  5. Jartti T, Paul-Anttila M, Lehtinen P, Parikka V, Vuorinen T, Simell O, Ruuskanen O. Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study. Respir Res 2009;10(1):85.

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Susetta Finotto
Professor Finotto (Department of Molecular Pulmonology) has provided major contributions to the field of lung immunology including the discovery of the role of T-bet in allergic asthma and lung cancer. Furthermore, she analyzed the role of the Th2 transcription factor GATA3 in asthma and identified IL-6 as a major factor controlling lung regulatory T cell development. She has long term experience in mouse models of lung diseases and is capable to perform lung cell isolation and invasive plethysmography.
Tasks in the project
Within Predicta, UKER team will recruit and follow up patients for the cohort (WP1), evaluate repeated RV infection in a T-bet knockout mouse model (WP2), provide material for virus-bacterial interactions studies (WP4) and provide patient material for immunological studies  (WP5)
Team members
Key staff involved include Caroline Übel, PhD student (expertise in lung molecular biology).
Relevant publications

  1. Maxeiner JH, Karwot R, Sauer K, Scholtes P, Boross I, Koslowski M, Türeci O, Wiewrodt R, Neurath MF, Lehr HA, Finotto S. A key regulatory role of the transcription factor NFATc2 in bronchial adenocarcinoma via CD8+ T lymphocytes. Cancer Res. 2009 Apr 1;69(7):3069-76.
  2. Doganci A, Karwot R, Maxeiner JH, Scholtes P, Schmitt E, Neurath MF, Lehr HA, Ho IC, Finotto S.   IL-2 receptor beta-chain signaling controls immunosuppressive CD4+ T cells in the draining lymph nodes and lung during allergic airway inflammation in vivo. J Immunol. 2008 Aug 1;181(3):1917-26.
  3. Doganci A, Eigenbrod T, Krug N, De Sanctis GT, Hausding M, Erpenbeck VJ, Haddad el-B, Lehr HA, Schmitt E, Bopp T, Kallen KJ, Herz U, Schmitt S, Luft C, Hecht O, Hohlfeld JM, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Rose-John S, Renz H, Neurath MF, Galle PR, Finotto S. The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J Clin Invest. 2005 Feb;115(2):313-25
  4. Finotto S, Neurath MF, Glickman JN, Qin S, Lehr HA, Green FH, Ackerman K, Haley K, Galle PR, Szabo SJ, Drazen JM, De Sanctis GT, Glimcher LH. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science. 2002 Jan 11;295(5553):336-8.
  5. Finotto S, De Sanctis GT, Lehr HA, Herz U, Buerke M, Schipp M, Bartsch B, Atreya R, Schmitt E, Galle PR, Renz H, Neurath MF. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J Exp Med. 2001 Jun 4;193(11):1247-60

stolz 
This email address is being protected from spambots. You need JavaScript enabled to view it. Stolz

Dr Frank Stolz, is responsible for the development of novel innovative allergy vaccines, the preclinical studies and the demonstration of the safety and efficacy of the new vaccines in clinical trials. 
Tasks in the project
BIOMAY will contribute to the diagnostic assay development in WP 7.
Relevant publications

  1. Stolz F, Panzer S, Fischer S, Panzer-Grumayer ER. Oligoclonal immunoglobulin heavy-chain and T-cell receptor delta rearrangements persist in a recurrent acute lymphoblastic leukemia with one immunoglobulin kappa rearrangement as a clonal marker. Mod Pathol 1999 Aug;12(8):819-26
  2. An De Creus, Katrien Van Beneden, Tom Taghon, Frank Stolz, Veronique Debacker, Jean Plum and Georges Leclercq. Langerhans cells which have matured in vivo in the absence of T cells are fully capable of inducing a CD4 as well as a cytotoxic CD8 response. The Journal of Immunology, 2000, 165: 645-653
  3. Tom Thagon, Magda De Smedt, Frank Stolz, Maggy Cnockaert, Jean Plum and Georges Leclerq. Enforced expression of GATA-3 severely reduces human thymic cellularity by disturbing TCR beta-chain expression and bypasses beta-selection. J Immunol. 2001 Oct 15;167(8):4468-75
  4. Stolz F, Panzer S, Panzer-Grumayer ER. Multiplex PCR reaction for the detection and identification of immunoglobulin kappa deleting element rearrangements in B-lineage leukemias. Br J Haematol 1999 Aug;106(2):486-90
  5. Dworzak MN, Stolz F, Froschl G, Printz D, Henn T, Fischer S, Fleischer C, Haas OA, Fritsch G, Gadner H, Panzer-Grumayer ER. Detection of residual disease in pediatric B-cell precursor acute lymphoblastic leukemia by comparative phenotype mapping: a study of five cases controlled by genetic methods. Exp Hematol 1999 Apr;7(4):673-81

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Dahlia Fasquel
Dahlia Fasquel holds a Master in Business law as well as the French Bar Exam. She joined Inserm Transfert’s Department of European and International affairs (DAEI) in 2004 and has a strong expertise in the management of European Projects, in particular on the financial rules and contractual aspects of the EU FP programmes.
Tasks in the project
Inserm-Transfert SA will be responsible for the management of the PreDicta consortium and for the co-ordination of the dissemination and exploitation of foreground and management of Intellectual property (WP9).
Team members
Inserm Transfert team includes Denise Hirsch (director of IP department with a 20 year-experience in IP management in life sciences), Laure Masson (Legal counsel) and Sandrine Graff (Assistant).

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Tuomas Jartti
Tuomas Jartti is Pediatric allergist at Turku University Hospital. The research focus of his group is the predisposition to respiratory viral infections (in particular Rhinovirus infection) and its relation to recurrent wheezing and later development of asthma.
Tasks in the project
The Department of Pediatrics participates in the pediatric cohort (WP1) and collections of clinical samples for WP4 and WP5 and in the analysis of bacterial colonization samples (WP4).
Team members
Key staff involved include Prof Olli Ruuskanen MD PHD (Senior scientist/consultant, expertise in Pediatr. Infect. Diseases) and Tytti Vuorinen (Head of virus laboratory, University of Turku, expertise in Clinical microbiology).
Relevant publications

  1. Jartti T, van den Hoogen B, Garofalo RP, Osterhaus ADME, O Ruuskanen. New human metapneumovirus and acute wheezing in children. Lancet 2002;360:1393-4.
  2. Jartti T, Lehtinen P, Vuorinen T, Österbacka R, van den Hoogen B, Osterhaus ADME, Ruuskanen O. Respiratory picornaviruses and respiratory syncytial virus are the major causative agents of acute expiratory wheezing in children. Emerg Infect Dis 2004;10:1095-101.
  3. Allander T, Jartti T, Gupta S, Niesters H, Lehtinen P, Österback R, Vuorinen T, Waris M, Tivejung-Lindell A, van den Hoogen B, Hyypiä T, Osterhaus A, Ruuskanen O. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904-10.
  4. Jartti T, Lee WM, Pappas T, Lemanske RF Jr, Gern JE. Serial viral infections in infants with recurrent respiratory illnesses Eur Respir J 2008;32:314-20.
  5. Jartti T, Paul-Anttila M, Lehtinen P, Parikka V, Vuorinen T, Simell O, Ruuskanen O. Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study. Respir Res 2009;10(1):85.
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3.