Renal allograft rejection: beta-chemokine involvement in the development of tubulitis.
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 beta-chemokines (MCP-1, MIP-1alpha, MIP-1beta, and RANTES) by immunofluorescence and semiquantitative confocal laser scanning microscopy.


RESULTS
Beta-chemokines were expressed predominantly at the basolateral surface of tubular epithelial cells. Expression of MCP-1 and MIP-1beta was significantly higher in sections showing grade 2 rather than grade 1 acute rejection. RANTES and MIP-1alpha showed no significant variation in level of expression between rejection grades.


CONCLUSIONS
Beta-chemokines are expressed by tubular epithelial cells during acute rejection. Consistent expression of RANTES and MIP-1alpha suggests a general role in recruiting T lymphocytes. However, MCP-1 and MIP-1beta may play a more subtle role in recruitment of specific T-cell subsets, such as Th1 cells, during acute cellular rejection.
Robertson
H
H
Department of Pathology, University of Newcastle upon Tyne, United Kingdom. helen.robertson@ncl.ac.uk
Morley
A R
AR
Talbot
D
D
Callanan
K
K
Kirby
J A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology; D002648:Child; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology*; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009393:Nephritis / Q000209:etiology
D019742:Chemokines, CC; D007166:Immunosuppressive Agents; D008775:Methylprednisolone