Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation

Elbert Kuo, Ankit Bharat, Trudie Goers, Will Chapman, Le Yan, Tyler Street, Wei Lu, Michael Walter, Alexander Patterson, Thalachallour Mohanakumar*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Methods: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-γ ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Results: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-γ producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Conclusions: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Original languageEnglish (US)
Pages (from-to)1043-1050
Number of pages8
JournalAnnals of Thoracic Surgery
Volume82
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Virus Diseases
Respiratory Tract Infections
Sendai virus
Transplantation
Allografts
Bronchiolitis Obliterans
Fibrosis
Immunosuppression
Interferons
Community-Acquired Infections
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Paramyxoviridae Infections
Lung Transplantation
Infection
Inbred C57BL Mouse
Cartilage
Immunization
Mucous Membrane
Vaccination

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Kuo, Elbert ; Bharat, Ankit ; Goers, Trudie ; Chapman, Will ; Yan, Le ; Street, Tyler ; Lu, Wei ; Walter, Michael ; Patterson, Alexander ; Mohanakumar, Thalachallour. / Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation. In: Annals of Thoracic Surgery. 2006 ; Vol. 82, No. 3. pp. 1043-1050.
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abstract = "Background: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Methods: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-γ ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Results: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-γ producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Conclusions: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.",
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Kuo, E, Bharat, A, Goers, T, Chapman, W, Yan, L, Street, T, Lu, W, Walter, M, Patterson, A & Mohanakumar, T 2006, 'Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation', Annals of Thoracic Surgery, vol. 82, no. 3, pp. 1043-1050. https://doi.org/10.1016/j.athoracsur.2006.03.120

Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation. / Kuo, Elbert; Bharat, Ankit; Goers, Trudie; Chapman, Will; Yan, Le; Street, Tyler; Lu, Wei; Walter, Michael; Patterson, Alexander; Mohanakumar, Thalachallour.

In: Annals of Thoracic Surgery, Vol. 82, No. 3, 01.09.2006, p. 1043-1050.

Research output: Contribution to journalArticle

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T1 - Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation

AU - Kuo, Elbert

AU - Bharat, Ankit

AU - Goers, Trudie

AU - Chapman, Will

AU - Yan, Le

AU - Street, Tyler

AU - Lu, Wei

AU - Walter, Michael

AU - Patterson, Alexander

AU - Mohanakumar, Thalachallour

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Background: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Methods: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-γ ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Results: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-γ producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Conclusions: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

AB - Background: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Methods: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-γ ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Results: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-γ producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Conclusions: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

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