Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-γ expression in pulmonary lymph of experimentally infected calves

Laurel J. Gershwin Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Robert A. Gunther Department of Surgery, School of Medicine, University of California, Davis, CA 95616.

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Mark L. Anderson California Veterinary Diagnostic Laboratory, Davis, CA 95616.

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Amelia R. Woolums Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.
present address is the Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Kerrie McArthur-Vaughan Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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K. Erin Randel Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Gabrielle A. Boyle Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Kathleen E. Friebertshauser Departments of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Pat S. McInturff Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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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.

Animals—Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data.

Procedure—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-γ 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-γ was variably present in infected and control calves, with IL-4 expression most consistent during early infection.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2000;61:291–298)

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.

Animals—Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data.

Procedure—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-γ 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-γ was variably present in infected and control calves, with IL-4 expression most consistent during early infection.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2000;61:291–298)

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