Tubulitis and epithelial cell alterations in mouse kidney transplant rejection are independent of CD103, perforin or granzymes A/B.
Am J Transplant
; 6(9): 2109-20, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16869802
ABSTRACT
One of the defining lesions of kidney allograft rejection is epithelial deterioration and invasion by inflammatory cells (tubulitis). We examined epithelial changes and their relationship to effector T cells and to CD103/E-cadherin interactions in mouse kidney allografts. Rejecting allografts showed interstitial mononuclear infiltration from day 5. Loss of epithelial mass, estimated by tubular surface area, and tubulitis were minimal through day 7 and severe by day 21. Tubules in day 21 allografts manifested severe reduction of E-cadherin and Ksp-cadherin by immunostaining with redistribution to the apical membrane, indicating loss of polarity. By flow cytometry T cells isolated from allografts were 25% CD103+. Laser capture microdissection and RT-PCR showed increased CD103 mRNA in the interstitium and tubules. However, allografts in hosts lacking CD103 developed tubulitis, cadherin loss, and epithelial deterioration similar to wild-type hosts. The loss of cadherins and epithelial mass was also independent of perforin and granzymes A and B. Thus rejection is characterized by severe tubular deterioration associated with CD103+ T cells but not mediated by CD103/cadherin interactions or granzyme-perforin cytotoxic mechanisms. We suggest that alloimmune effector T cells mediate epithelial injury by contact-independent mechanisms related to delayed type hypersensitivity, followed by invasion of the altered epithelium to produce tubulitis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Antígenos CD
/
Transplante de Rim
/
Cadeias alfa de Integrinas
/
Células Epiteliais
/
Rejeição de Enxerto
/
Túbulos Renais
/
Proteínas de Membrana
/
Nefrite
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Canadá