PMID- 22154724
OWN - NLM
STAT- MEDLINE
DCOM- 20120813
LR  - 20211021
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 73
IP  - 2
DP  - 2012 Feb
TI  - Favorable effects of alemtuzumab on allospecific regulatory T-cell generation.
PG  - 141-9
LID - 10.1016/j.humimm.2011.11.008 [doi]
AB  - We studied the effects of alemtuzumab on T-regulatory cells (Tregs) during 
      alloactivation, first by differences in depletion of various naive versus 
      alloactivated cell subsets in peripheral blood of healthy volunteers, then by 
      adding serial concentrations to human leukocyte antigen (HLA)-DR-matched and 
      -mismatched responding and stimulating cells in mixed lymphocyte reaction (MLR). 
      Lymphoproliferation inhibition and the development of proliferating 
      carboxyfluorescein succinimidyl ester (CFSE)-diluted 
      CD4(+)CD25(high)CD127(-)FOXP3(+) (phenotypic) Tregs by flow cytometry were 
      measured. Also, the ability of alemtuzumab-treated versus nontreated MLR 
      generated CD4(+)CD127(-) cells to allospecifically inhibit MLRs and recruit 
      additional responding Tregs was tested. We found a more pronounced refractoriness 
      of alloactivated versus naive CD4(+)CD25(high) cells to alemtuzumab induced 
      lymphodepletion. Alemtuzumab dose dependently inhibited lymphoproliferation while 
      amplifying percentages of MLR-generated Tregs. This was somewhat augmented by 
      human complement addition. CD127(-)CD4(+) cells immunoselected after 7 days from 
      alemtuzumab-treated MLRs allospecifically inhibited lymphoproliferation and 
      recruited additional Tregs in fresh MLR-responding cells, similar to modulators 
      derived from MLRs without drug addition (media). Addition of tacrolimus and 
      sirolimus to alemtuzumab further inhibited MLR proliferation. However, Treg 
      percentages were markedly higher with sirolimus. These results support the notion 
      that alemtuzumab induces immunoregulation in naive T cells undergoing 
      alloactivation absent presensitization, especially used in conjunction with 
      maintenance SRL.
CI  - Copyright (c) 2012 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Levitsky, Josh
AU  - Levitsky J
AD  - Division of Gastroenterology, Hepatology, Department of Medicine, Northwestern 
      University, Feinberg School of Medicine, Chicago, Illinois, USA.
FAU - Leventhal, Joseph R
AU  - Leventhal JR
FAU - Miller, Joshua
AU  - Miller J
FAU - Huang, Xuemei
AU  - Huang X
FAU - Chen, Li
AU  - Chen L
FAU - Chandrasekaran, Dhivya
AU  - Chandrasekaran D
FAU - Tambur, Anat R
AU  - Tambur AR
FAU - Mathew, James M
AU  - Mathew JM
LA  - eng
GR  - R01 DK025243/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000150/TR/NCATS NIH HHS/United States
GR  - 2R01DK25243-25A2/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111123
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 3A189DH42V (Alemtuzumab)
SB  - IM
MH  - Alemtuzumab
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Humans
MH  - T-Lymphocytes, Regulatory/cytology/*drug effects/immunology
PMC - PMC4064370
MID - NIHMS597682
EDAT- 2011/12/14 06:00
MHDA- 2012/08/14 06:00
PMCR- 2014/06/20
CRDT- 2011/12/14 06:00
PHST- 2011/08/15 00:00 [received]
PHST- 2011/10/12 00:00 [revised]
PHST- 2011/11/07 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/08/14 06:00 [medline]
PHST- 2014/06/20 00:00 [pmc-release]
AID - S0198-8859(11)00581-7 [pii]
AID - 10.1016/j.humimm.2011.11.008 [doi]
PST - ppublish
SO  - Hum Immunol. 2012 Feb;73(2):141-9. doi: 10.1016/j.humimm.2011.11.008. Epub 2011 
      Nov 23.