TY - JOUR
T1 - Predominant Th1 and cytotoxic phenotype in biopsies from renal transplant recipients with transplant glomerulopathy
AU - Homs, S.
AU - Mansour, H.
AU - Desvaux, D.
AU - Diet, C.
AU - Hazan, M.
AU - Buchler, M.
AU - Lebranchu, Y.
AU - Buob, D.
AU - Badoual, C.
AU - Matignon, M.
AU - Audard, V.
AU - Lang, P.
AU - Grimbert, P.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INFγ), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and RORγt) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function. Only INFγ, T-bet (both functionally defined markers of Th1 CD4 T cells) and granzyme B (a CD8 cytotoxic marker) were significantly more strongly expressed in patients with TGP than in patients without TGP and normal controls. These results indicate a role of an active T-mediated inflammatory and cytotoxic process in the pathogenesis of TGP.
AB - Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INFγ), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and RORγt) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function. Only INFγ, T-bet (both functionally defined markers of Th1 CD4 T cells) and granzyme B (a CD8 cytotoxic marker) were significantly more strongly expressed in patients with TGP than in patients without TGP and normal controls. These results indicate a role of an active T-mediated inflammatory and cytotoxic process in the pathogenesis of TGP.
KW - Chronic transplant glomerulopathy
KW - Immune function
KW - Renal transplant
KW - Renal transplant pathology
UR - http://www.scopus.com/inward/record.url?scp=65249177814&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2009.02596.x
DO - 10.1111/j.1600-6143.2009.02596.x
M3 - Article
C2 - 19422348
AN - SCOPUS:65249177814
SN - 1600-6135
VL - 9
SP - 1230
EP - 1236
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -