Innate and adaptive immune responses in obliterative XXXX in @entity35 tracheal allografts.

@entity63 @entity205 @entity22140 @entity432 @entity1030 @entity35
BACKGROUND: We assessed cellular innate and adaptive immune responses in a @entity35 heterotopic tracheal allograft model during the development of obliterative @entity1030 . METHODS: Syngeneic tracheal grafts were transplanted heterotopically from DA to DA @entity35 and fully MHC-mismatched allografts from DA to WF @entity35 . The recipients received either no immunosuppression or two different doses of @entity205 and were euthanized at 3, 10 and 30 days. Non-transplanted DA tracheas served as controls. Histologic, immunohistochemical and real-time RT-PCR analyses were performed. RESULTS: The syngrafts had normal epithelium at 10 days and no @entity432 was seen at 30 days. In non-immunosuppressed allografts, almost total loss of epithelium was observed at 10 days, culminating in @entity432 at 30 days. The activation of innate immune response was observed during the ischemic period at 3 days in both groups. Influx of the infiltrating inflammatory cells was more prominent in the allografts. In syngrafts, mRNA expression of pro-inflammatory, but also tolerogenic, cytokines was significantly upregulated, whereas Th1 and Th17 priming factors were significantly downregulated. In allografts, prominent mRNA expression of pro-inflammatory cytokines was seen and adaptive Th1 and Th17 alloresponses were increased. @entity205 treatment reduced @entity432 and inhibited both tolerogenic and pro-inflammatory T-cell responses in allografts. CONCLUSIONS: @entity63 induced a self-limiting, alloantigen-independent innate immune response in syngrafts. In allografts, the predominant pro-inflammatory milieu and @entity22140 -dependent Th1 and Th17 responses were linked to the development of obliterative @entity1030 and were inhibited by @entity205 treatment.
