TY - JOUR
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
N1 - Funding Information:
This work was supported by NIH/RO1-HL66452 (TM) and NIH/T32-AI07163 (EK). The authors would like to express their thanks to Billie Glasscock and Dr Celeste Kuo for their assistance in preparing this manuscript, and to Dr Richard Schuessler for his statistical analysis of our data.
PY - 2006/9
Y1 - 2006/9
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.
UR - http://www.scopus.com/inward/record.url?scp=33747378503&partnerID=8YFLogxK
U2 - 10.1016/j.athoracsur.2006.03.120
DO - 10.1016/j.athoracsur.2006.03.120
M3 - Article
C2 - 16928532
AN - SCOPUS:33747378503
SN - 0003-4975
VL - 82
SP - 1043
EP - 1050
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 3
ER -