Renal allograft rejection - beta-chemokine involvement in the development of tubulitis

Background. Tubulitis is a defining feature of renal allograft rejection. G raft dysfunction may result from damage inflicted on tubular epithelial cel ls by intratubular cytotoxic T lymphocytes. Graft cells are known to produc e chemokines during acute rejection, but it is not known whether changes in expression of specific chemokines can influence the composition of the int ratubular lymphocyte population. We examined expression of individual chemo kines in biopsy sections showing different pathological rejection grades. Methods. Sections from Banff-graded transplant biopsies were examined for t he presence of beta-chemokines (MCP-1, MIP-l alpha, MIP-1 beta, and RANTES) by immunofluorescence and semiquantitative confocal laser scanning microsc opy, Results. beta-Chemokines were expressed predominantly at the basolateral su rface of tubular epithelial cells. Expression of MCP-1 and MIP-1 beta was s ignificantly higher in sections showing grade 2 rather than grade 1 acute r ejection, RANTES and MIP-l alpha showed no significant variation in level o f expression between rejection grades, Conclusions. beta-Chemokines are expressed by tubular epithelial cells duri ng acute rejection. Consistent expression of RANTES and MIP-1 alpha suggest s a general role in recruiting T lymphocytes, However, MCP-1 and MIP-1 beta may play a more subtle role in recruitment of specific T cell subsets, suc h as Th1 cells, during acute cellular rejection.