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Tubulitis in renal allograft rejection: Role of transforming growth factor-β and interleukin-15 in development and maintenance of CD103+ intraepithelial T cells

Lookup NU author(s): Dr Helen Robertson, Helen Carroll, Professor Simi Ali, Professor John Kirby

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Abstract

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.


Publication metadata

Author(s): Wong WK, Robertson H, Carroll HP, Ali S, Kirby JA

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2003

Volume: 75

Issue: 4

Pages: 505-514

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/01.TP.0000045708.39879.C7

DOI: 10.1097/01.TP.0000045708.39879.C7

PubMed id: 12605119


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