Tim-3 expression in human kidney allografts.
BACKGROUND
Tim-3 was recently described as a Th1-specific molecule, participating in the regulation of immune responses and in the induction of allograft tolerance. Here, we studied Tim-3 mRNA expression together with molecular markers of T-cell activation and cytotoxicity, in rejected human kidney grafts.


METHODS
Twenty human kidney grafts that had undergone nephrectomy due to an irreversible acute rejection episode were studied. We quantified intragraft expression of Tim-3, granzyme B, perforin, IFN-gamma and Fas-ligand mRNA by real-time RT-PCR, with probes and primers TaqMan. Protocol biopsies were studied as controls. Statistical analyses were performed to compare groups, and to investigate the potential association with gene transcripts measures and rejection.


RESULTS
All molecules studied were up-regulated in the rejection group compared with controls (p<0.001). Acute rejection type III (Banff 97) profiles were associated with higher values, where granzyme B and perforin presented the highest (5672.51+/-9002.16 and 1866.59+/-2426.38, respectively) and Tim-3 had the lowest ones (166.62+/-174.94). Tim-3 had also a lower expression in those patients that did not respond to anti-rejection therapy. There was a positive correlation between Tim-3 and IFN-gamma mRNA expression levels (r(2)=0.73; p<0.001).


CONCLUSIONS
Our results corroborate the concept that acute rejection is an active process, where inflammatory as well as regulatory factors have their roles. Severe episodes of acute rejection were associated with higher expression of cytotoxic molecules and lower expression of potential regulatory molecule.
Ponciano
Viviane C
VC
Laboratory of Clinical and Experimental Immunology, Nephrology Division, Universidade Federal de São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900, São Paulo, SP, Brazil.
Renesto
Paulo G
PG
Nogueira
Eliana
E
Rangel
Erika B
EB
Cenedeze
Marcos A
MA
Franco
Marcello F
MF
Câmara
Niels O S
NO
Pacheco-Silva
Alvaro
A
D000328:Adult; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D053804:Granzymes / Q000096:biosynthesis; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D011991:Receptors, Virus / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes