PMID- 23222818
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20211203
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 95
IP  - 1
DP  - 2013 Jan 15
TI  - Everolimus-treated renal transplant recipients have a more robust CMV-specific 
      CD8+ T-cell response compared with cyclosporine- or mycophenolate-treated 
      patients.
PG  - 184-91
LID - 10.1097/TP.0b013e318276a1ef [doi]
AB  - BACKGROUND: In renal transplant recipients, mammalian target of rapamycin (mTOR) 
      inhibitors have been reported to protect against cytomegalovirus (CMV) disease. 
      Here, we questioned whether mTOR inhibitors specifically influence human 
      CMV-induced T-cell responses. METHODS: We studied renal transplant recipients 
      treated with prednisolone, cyclosporine A (CsA), and mycophenolate sodium (MPS) 
      for the first 6 months after transplantation followed by double therapy 
      consisting of prednisolone/everolimus, which is an mTOR inhibitor (P/EVL; n=10), 
      prednisolone/CsA (P/CsA; n=7), or prednisolone/MPS (P/MPS; n=9). All patients 
      were CMV-IgG positive before transplantation. CMV reactivation was detectable in 
      the first 6 months after transplantation and not thereafter. None of the patients 
      included in this study suffered from CMV disease. Both CD27CD8 and CD27CD28CD4 
      effector-type T-cell counts, known to be associated with CMV infection, were 
      measured before transplantation and at 6 and 24 months after transplantation. 
      Additionally, we determined both number and function of CMV-specific CD8 T cells 
      at these time points. RESULTS: The number of total CD8 T cells, CD27CD8 T cells, 
      and CD28CD4 T cells increased significantly after switch to therapy with P/EVL 
      but not after switch to P/CsA or P/MPS. Specifically, CMV-specific CD8 T-cell 
      counts significantly increased after switch to therapy with P/EVL. Furthermore, 
      the mTOR inhibitor sirolimus strongly inhibited alloresponses in vitro, whereas 
      it did not affect CMV-specific responses. CONCLUSION: We observed a significant 
      increase in (CMV-specific) effector-type CD8 and CD4 T-cell counts in 
      everolimus-treated patients. These findings may at least in part explain the 
      reported low incidence of CMV-related pathology in everolimus-treated patients.
FAU - Havenith, Simone H C
AU  - Havenith SH
AD  - Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, 
      Amsterdam, The Netherlands. s.h.havenith@amc.uva.nl
FAU - Yong, Si La
AU  - Yong SL
FAU - van Donselaar-van der Pant, Karlijn A M I
AU  - van Donselaar-van der Pant KA
FAU - van Lier, Rene A W
AU  - van Lier RA
FAU - ten Berge, Ineke J M
AU  - ten Berge IJ
FAU - Bemelman, Frederike J
AU  - Bemelman FJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cyclosporine/*pharmacology
MH  - Cytomegalovirus/*immunology
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - *Kidney Transplantation
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/*analogs & derivatives/pharmacology
MH  - Prednisolone/pharmacology
MH  - Sirolimus/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
EDAT- 2012/12/12 06:00
MHDA- 2013/04/04 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
AID - 10.1097/TP.0b013e318276a1ef [doi]
PST - ppublish
SO  - Transplantation. 2013 Jan 15;95(1):184-91. doi: 10.1097/TP.0b013e318276a1ef.