title: Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-gamma expression in pulmonary lymph of experimentally infected calves.
abstract: OBJECTIVE
  To study the local immune response of calves to bovine respiratory syncytial virus (BRSV) infection with emphasis on IgE production and cytokine gene expression in pulmonary lymph.
  
  
  METHODS
  Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data.
  
  
  METHODS
  Lymphatic cannulation surgery was performed on 12 calves to create a long-term thoracic lymph fistula draining to the exterior. Cannulated calves were exposed to virulent BRSV by aerosol. Lymph fluid collected daily was assayed for BRSV and isotype-specific IgE antibody, total IgG, IgA, IgM, and protein concentrations. Interleukin-4 (IL-4), interleukin-2 (IL-2), and interferon-gamma were semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). Cell counts and fluorescence-activated cell scanner (FACSCAN) analysis of T-cell subsets were performed on lymph cells.
  
  
  RESULTS
  Calves had clinical signs of respiratory tract disease during days 5 to 10 after infection and shed virus. Bovine respiratory syncytial virus-specific IgE in infected calves was significantly increased over baseline on day 9 after infection. Mean virus-specific IgE concentrations strongly correlated with increases in severity of clinical disease (r = 0.903). Expression of IL-2, IL-4, and interferon-gamma was variably present in infected and control calves, with IL-4 expression most consistent during early infection.
  
  
  CONCLUSIONS
  Infection with BRSV was associated with production of BRSV-specific IgE, and IL-4 message was commonly found in lymph cells of infected calves. This finding supports the concept that BRSV-induced pathophysiology involves a T helper cell type-2 response. Effective therapeutic and prophylactic strategies could, therefore, be developed using immunomodulation to shift the immune response more toward a T helper cell type-1 response.
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of California, Davis 95616, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Gershwin
authors.forename: R A
authors.initials: RA
authors.lastname: Gunther
authors.forename: M L
authors.initials: ML
authors.lastname: Anderson
authors.forename: A R
authors.initials: AR
authors.lastname: Woolums
authors.forename: K
authors.initials: K
authors.lastname: McArthur-Vaughan
authors.forename: K E
authors.initials: KE
authors.lastname: Randel
authors.forename: G A
authors.initials: GA
authors.lastname: Boyle
authors.forename: K E
authors.initials: KE
authors.lastname: Friebertshauser
authors.forename: P S
authors.initials: PS
authors.lastname: McInturff
mesh_terms: D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D002404:Catheterization / Q000662:veterinary; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000821:virology; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004587:Electrophoresis, Agar Gel / Q000662:veterinary; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005434:Flow Cytometry / Q000662:veterinary; D005620:Freund's Adjuvant / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000473:pathology; D008196:Lymph / Q000737:chemistry / Q000276:immunology; D008297:Male; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000662:veterinary*; D018112:Respiratory Syncytial Virus, Bovine / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D017931:DNA Primers; D007376:Interleukin-2; D015847:Interleukin-4; D012313:RNA; D007371:Interferon-gamma; D004247:DNA; D005620:Freund's Adjuvant