Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.
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-gamma 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-gamma 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.
Kuo
Elbert
E
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA.
Bharat
Ankit
A
Goers
Trudie
T
Chapman
Will
W
Yan
Le
L
Street
Tyler
T
Lu
Wei
W
Walter
Michael
M
Patterson
Alexander
A
Mohanakumar
Thalachallour
T
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D005355:Fibrosis; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000209:etiology* / Q000821:virology; D012141:Respiratory Tract Infections / Q000150:complications* / Q000821:virology; D010253:Respirovirus Infections / Q000150:complications*; D029082:Sendai virus / Q000276:immunology; D013997:Time Factors; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014765:Viral Vaccines / Q000276:immunology
D014765:Viral Vaccines