Peripheral expansion of circulating T-helper 1 cells predicts coronary endothelial dysfunction after cardiac transplantation.
OBJECTIVE
We sought to assess the importance of Th1 cells for the development of cardiac allograft vasculopathy.


BACKGROUND
Despite improvements in immunosuppressive regimens, chronic rejection still represents one of the leading causes of death beyond the first year after heart transplantation. Chronic rejection is characterized by the development of transplant vasculopathy. The exact mechanisms initiating and promoting this form of arteriosclerosis in the human setting remain unclear.


METHODS
In order to assess the role of T lymphocytes we characterized differentiated T-cell subsets in 32 transplant recipients early after transplantation using RT-PCR, flow cytometry and immunhistochemistry and matched these findings with endothelial function testing as an early clinical indicator of transplant vasculopathy.


RESULTS
Allograft endothelial dysfunction (ED) was defined as a compromised coronary flow reserve to acetylcholine (CFVR<2 in 8 of 32 transplant recipients). In these patients, mRNA transcript levels for the T-helper (Th)1 signature cytokines interferon (INF)-gamma (p<0.0001) and interleukin (IL)-2 (p<0.005) and STAT4 (Th1 transcription factor, p<0,05) were significantly higher than in the remaining 24 patients with normal endothelial function. This correlated with a significant increase in circulating CD3(+)/IFN-gamma(+)-T-cells (28.6 +/- 4.4% vs 8.7 +/- 5.6%; p<0.0001). In contrast, transcript levels for the Th2 signature cytokines (IL-4, IL-10) and STAT6 (Th2 transcription factor) did not differ significantly between the two groups.


CONCLUSIONS
Peripheral expansion of circulating Th1 but not Th2 cells predicts coronary ED after cardiac transplantation. Therefore, quantification of circulating T cells might be a diagnostic tool to predict development of ED in patients after heart transplantation.
Department of Cardiology, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany. heiko.methe@med.uni-muenchen.de
Heiko
H
Methe
Daniela
D
Wiegand
Ulrich
U
Welsch
Fritz
F
Krombach
Bruno
B
Meiser
Michael
M
Nabauer
Joerg
J
Koglin
D017023:Coronary Angiography; D003326:Coronary Circulation; D016207:Cytokines / Q000032:analysis; D018076:DNA, Complementary / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger