PMID- 20970555
OWN - NLM
STAT- MEDLINE
DCOM- 20110328
LR  - 20220330
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 42
IP  - 8
DP  - 2010 Oct
TI  - Number of peripheral blood regulatory T cells and lymphocyte activation at 3 
      months after conversion to mTOR inhibitor therapy.
PG  - 2871-3
LID - 10.1016/j.transproceed.2010.07.045 [doi]
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are effective for 
      induction and maintenance of regulatory T cells (Tregs). OBJECTIVE: To assess the 
      effects of conversion from calcineurin inhibitors (CNIs) to mTOR on the number of 
      circulating Tregs and lymphocyte activation. PATIENTS AND METHODS: In 18 renal 
      transplant recipients receiving CNI therapy (cyclosporine in 9, and tacrolimus in 
      9), treatment was converted to mTOR inhibitors (everolimus in 14, and rapamycin 
      in 4). Peripheral blood samples were obtained before and 3 months after 
      conversion. The number of circulating Tregs was measured using flow cytometry, 
      and defined as CD4+/CD25high/CD127low/CD27+/CD62L+/CD45RO+/Foxp3+. Lymphocyte 
      activation was assessed indirectly according to production of intracellular 
      adenosine triphosphate (iATP) on polyclonal activation using a phytohemaglutinin 
      assay (Immuknow; Cylex, Inc, Columbia, Maryland). RESULTS: In 15 patients 
      (83.3%), the absolute number of Tregs increased significantly (P=.001) after 
      conversion (median, 16.35 cells/mm3; 95% confidence interval [CI], 13.97-21.94) 
      vs 3 months after conversion (32.03 cells/mm3; 95% CI, 26.25-41.66). The iATP 
      production decreased from 326 ng/mL (95% CI, 302-419) to 248 ng/mL (95% CI, 
      196-318; P=.02), and increased in 4 patients (22.22%). No significant correlation 
      was demonstrated between Treg concentration and change in iATP production. No 
      rejection episodes were reported during follow-up. CONCLUSIONS: Despite the small 
      number of patients in whom therapy was converted from CNI inhibitors to mTOR 
      inhibitors, the data suggest an increase in the absolute number of Tregs after 
      conversion. In addition, the concentration of activated peripheral CD4+ T cells 
      decreased to nearly that associated with risk of infection due to 
      overimmunosuppression.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - San Segundo, D
AU  - San Segundo D
AD  - Service of Immunology, Hospital Universitario Marques de Valdecilla, Instituto de 
      Formacion e Investigacion Marques de Valdecilla, Santander 39008, Spain.
FAU - Fernandez-Fresnedo, G
AU  - Fernandez-Fresnedo G
FAU - Gago, M
AU  - Gago M
FAU - Beares, I
AU  - Beares I
FAU - Ruiz-Criado, J
AU  - Ruiz-Criado J
FAU - Gonzalez, M
AU  - Gonzalez M
FAU - Ruiz, J C
AU  - Ruiz JC
FAU - Gomez-Alamillo, C
AU  - Gomez-Alamillo C
FAU - Arias, M
AU  - Arias M
FAU - Lopez-Hoyos, M
AU  - Lopez-Hoyos M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Immunophenotyping
MH  - *Lymphocyte Activation
MH  - T-Lymphocytes, Regulatory/*cytology/immunology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2010/10/26 06:00
MHDA- 2011/03/29 06:00
CRDT- 2010/10/26 06:00
PHST- 2010/10/26 06:00 [entrez]
PHST- 2010/10/26 06:00 [pubmed]
PHST- 2011/03/29 06:00 [medline]
AID - S0041-1345(10)01090-0 [pii]
AID - 10.1016/j.transproceed.2010.07.045 [doi]
PST - ppublish
SO  - Transplant Proc. 2010 Oct;42(8):2871-3. doi: 10.1016/j.transproceed.2010.07.045.