Role of CMV chemokine receptor M33 in airway graft rejection in a mouse transplant model

Background: Cytomegalovirus (CMV) infection is a risk factor for bronchiolitis obliterans (BO), one form of chronic lung allograft dysfunction (CLAD). The viral chemokine receptor M33 is essential for successful spread of murine CMV to host salivary glands. In the present study we investigated the impact of M33 on chronic airway rejection. Methods: MHC I-mismatched tracheas of C & sdot;B10-H2b/LilMcdJ mice were transplanted into BALB/c (H2d) recipients and infected at different dates with wild type (WT) or M33-deleted (delM33) MCMV representing clinical settings of viral recipient (R)-donor (D)-serostatus: (D-/R+) or (D+/R-). Grafts were recovered for gene expression and histological / immunofluorescence analysis, respectively. Results: Evaluations showed significantly increased signs of chronic rejection in WT-infected mice compared to uninfected allografts seen in lower epithelium/lamina propria-ratio (ELR) (ELR 0.46 +/- 0.07 [WT post] vs. ELR 0.66 +/- 0.10 [non-inf.]; p < 0.05). The rejection in delM33-infected groups was significantly reduced vs. WTinfected groups (0.67 +/- 0.04 [delM33 post]; vs. WT post p < 0.05). Furthermore, decreased rejection was observed in WT pre-infected compared to post-infected groups (0.56 +/- 0.08 [WT pre]; vs. WT post p < 0.05). CD8+ T cell infiltration was significantly higher in WT-post compared to the delM33 infected or non-infected allografts. Conclusions: These data support the role of the CMV in accelerating CLAD. The deletion of chemokine receptor M33 leads to attenuated rejection.

Automated summary

The study found that CMV infection accelerates chronic airway rejection, while deletion of the chemokine receptor M33 attenuates rejection.