RENAL ALLOGRAFT REJECTION

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Abstract
Background. Tubulitis is a defining feature of renal allograft rejection. Graft dysfunction may result from damage inflicted on tubular epithelial cells by intratubular cytotoxic T lymphocytes. Graft cells are known to produce chemokines during acute rejection, but it is not known whether changes in expression of specific chemokines can influence the composition of the intratubular lymphocyte population. We examined expression of individual chemokines in biopsy sections showing different pathological rejection grades. Methods. Sections from Banff-graded transplant biopsies were examined for the presence of β-chemokines (MCP-1, MIP-1α, MIP-1β, and RANTES) by immunofluorescence and semiquantitative confocal laser scanning microscopy. Results. β-Chemokines were expressed predominantly at the basolateral surface of tubular epithelial cells. Expression of MCP-1 and MIP-1β was significantly higher in sections showing grade 2 rather than grade 1 acute rejection. RANTES and MIP-1α showed no significant variation in level of expression between rejection grades. Conclusions. β-Chemokines are expressed by tubular epithelial cells during acute rejection. Consistent expression of RANTES and MIP-1α suggests a general role in recruiting T lymphocytes. However, MCP-1 and MIP-1β may play a more subtle role in recruitment of specific T-cell subsets, such as Th1 cells, during acute cellular rejection.