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Lookup NU author(s): Dr Helen Robertson,
Professor Simi Ali,
Emeritus Professor John Kirby
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Background. Renal tubules normally show no lymphocyte infiltration, but tubulitis is a feature of renal allograft rejection with many intratubular T cells expressing CD8 and CD103 (the αEβ7 integrin). We investigated the development and maintenance of allospecific CD103+ T cells within the tubular microenvironment. Methods. Mixed lymphocyte cultures were supplemented with transforming growth factor (TGF)-β1 to model the expression and function of CD103 observed in situ on intratubular lymphocytes. Immunocytochemical techniques were used to identify cells coexpressing CD8 and interleukin (IL)-15Rα, to enumerate proliferating intratubular T cells, and to quantify IL-15 expression within the tubules of control and rejection-graded transplant biopsy specimens. These results were compared with a parallel analysis of the phenotype and proliferation of allospecific T cells expanded in vitro in the presence of TGF-β1 and IL-15. Results. TGF-β1 only induced the expression of adhesive CD103 after at least one cycle of alloantigen-specific cell division in vitro. In the renal allograft, a similar proportion of intratubular T cells was observed to proliferate during and after acute rejection. Tubular epithelial cells expressed IL-15 constitutively, whereas intratubular CD8+ T cells expressed IL-15 receptor α. IL-15 and TGF-β1 synergized to promote expansion and survival of allospecific CD8+CD103+ T cells in vitro, but IL-15 down-regulated perforin expression. Conclusions. These results suggest that activated, allospecific CD8+ T cells are recruited to tubules during acute rejection where they encounter TGF-β, upregulate CD103 expression, and bind E-cadherin. A proportion of these cells proliferates and is maintained in a state of low perforin expression by the combined action of TGF-β and IL-15.
Author(s): Wong WK, Robertson H, Carroll HP, Ali S, Kirby JA
Publication type: Article
Publication status: Published
ISSN (print): 0041-1337
ISSN (electronic): 1534-6080
Publisher: Lippincott Williams & Wilkins
PubMed id: 12605119
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