Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-gamma expression in pulmonary lymph of experimentally infected calves.
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.
Gershwin
L J
LJ
Department of Pathology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Gunther
R A
RA
Anderson
M L
ML
Woolums
A R
AR
McArthur-Vaughan
K
K
Randel
K E
KE
Boyle
G A
GA
Friebertshauser
K E
KE
McInturff
P S
PS
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
D017931:DNA Primers; D007376:Interleukin-2; D015847:Interleukin-4; D012313:RNA; D007371:Interferon-gamma; D004247:DNA; D005620:Freund's Adjuvant