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Renal allograft rejection: The development and function of tubulitis

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

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Abstract

After renal transplantation a population of activated allospecific T cells can infiltrate the tubules during acute rejection. These T cells, which are predominantly CD8+, migrate under the influence of chemokines produced by tubular epithelial cells, and target the tubular epithelium specifically. Within the tubular epithelial microenvironment they encounter a range of cytokines including TGFβ1, which stimulates induction of the αEβ7 integrin (CD103), αEβ7 integrin stabilises T cell interaction with E-cadherin on the tubular epithelial cells. The close association maintained between donor antigen-specific intratubular T cells and antigen-expressing donor epithelial cells may result in damage to the tubular epithelial cells during acute rejection. However, it is possible that IL-15, which is also produced by tubular epithelial cells, can support long-term survival of a donor antigen-specific memory-like population of CD8+ T cells. Thus, focal lesions may be created that could promote tubulo-interstitial changes including fibrosis and, in the long term, cause chronic graft dysfunction. Tubulitis is clearly fundamental to defining the pathology of acute rejection. In this review we suggest that this inflammatory process can also result in the development of a long-lived population of immune cells within the tubules that could play an active role in promoting the development of chronic graft pathology. Therefore, factors that promote the recruitment and survival of allospecific lymphocytes within the tubular microenvironment are important targets to be considered for therapeutic intervention in both acute and chronic renal allograft rejection. Copyright © 2001 by W.B. Saunders Company.


Publication metadata

Author(s): Kirby JA; Robertson H

Publication type: Review

Publication status: Published

Journal: Transplantation Reviews

Year: 2001

Volume: 15

Issue: 3

Pages: 109-128

Print publication date: 01/01/2001

ISSN (print): 0955-470X

ISSN (electronic): 1557-9816

URL: http://dx.doi.org/10.1053/trre.2001.24499

DOI: 10.1053/trre.2001.24499


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