PMID- 19996930
OWN - NLM
STAT- MEDLINE
DCOM- 20091224
LR  - 20211020
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 88
IP  - 11
DP  - 2009 Dec 15
TI  - The human "Treg MLR": immune monitoring for FOXP3+ T regulatory cell generation.
PG  - 1303-11
LID - 10.1097/TP.0b013e3181bbee98 [doi]
AB  - BACKGROUND: Controversy exists about the conditions effecting the development of 
      forkhead/winghead helix transcription factor P3 (FOXP3) expressing T cells and 
      their relevance in transplant recipients. METHODS: We generated 
      carboxy-fluorescein diacetate succinimidyl ester-labeled CD4+CD25 high FOXP3+ 
      cells in mixed lymphocyte reactions (MLRs) ("the Treg MLR"), with varying human 
      leukocyte antigen (HLA) disparities and cell components. Five color flow 
      cytometry and H-thymidine uptakes were the readouts. RESULTS: (1) Despite lower 
      stimulation indices (SIs) than two DR-mismatched MLRs, 2 DR-matched MLRs 
      generated more than twofold higher percentages when gating on proliferating 
      CD4+CD25 high FOXP3+ cells; (2) Even with low numbers of proliferating cells, 
      autologous and HLA identical MLRs generated the highest FOXP3+:FOXP3- cell 
      ratios; (3) Elimination of either non-CD3+ responding cells (resulting in "direct 
      presentation" only) or responding CD25+ (Treg generating) cells increased the SI 
      but inhibited proliferating CD4+CD25 high FOXP3+ cell development; (4) 
      MLR-generated CD4+CD25 high FOXP3+ cells added as third components specifically 
      inhibited the same freshly set MLR SI and caused recruitment of new CD4+CD25 high 
      FOXP3+ cells. As an example of the "Treg MLR" immune monitoring potential, 
      addition of third component peripheral blood mononuclear cell containing high 
      percentages of CD4+CD25 high FOXP3+ cells from an HLA identical kidney transplant 
      recipient (in a tolerance protocol) caused donor-specific Treg MLR inhibition or 
      recruitment. This was similar to the third component MLR Tregs generated entirely 
      in vitro. CONCLUSION: In the Treg MLR, the generation of CD4+CD25 high FOXP3+ 
      cells is more pronounced in the context of self-recognition (HLA matching, 
      indirect presentation). These cells can be assayed for MLR inhibitory and Treg 
      recruitment functions, so as to immunologically monitor the allospecific 
      regulation after transplantation.
FAU - Levitsky, Josh
AU  - Levitsky J
AD  - Division of Hepatology, Department of Medicine, Northwestern University Feinberg 
      School of Medicine, Chicago, IL 60611, USA.
FAU - Miller, Joshua
AU  - Miller J
FAU - Leventhal, Joseph
AU  - Leventhal J
FAU - Huang, Xuemei
AU  - Huang X
FAU - Flaa, Cathy
AU  - Flaa C
FAU - Wang, Edward
AU  - Wang E
FAU - Tambur, Anat
AU  - Tambur A
FAU - Burt, Richard K
AU  - Burt RK
FAU - Gallon, Lorenzo
AU  - Gallon L
FAU - Mathew, James M
AU  - Mathew JM
LA  - eng
GR  - R01 DK025243/DK/NIDDK NIH HHS/United States
GR  - R01 DK025243-27/DK/NIDDK NIH HHS/United States
GR  - UL1 RR025741/RR/NCRR 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.
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (CD3 Complex)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (HLA Antigens)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
SB  - IM
MH  - Antigen Presentation
MH  - CD3 Complex/immunology
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Forkhead Transcription Factors/*immunology
MH  - HLA Antigens/immunology
MH  - Histocompatibility
MH  - Humans
MH  - Interleukin-2 Receptor alpha Subunit/immunology
MH  - Kidney Transplantation/*immunology
MH  - *Lymphocyte Culture Test, Mixed
MH  - Predictive Value of Tests
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Time Factors
MH  - *Transplantation Tolerance
PMC - PMC2792565
MID - NIHMS149508
EDAT- 2009/12/10 06:00
MHDA- 2009/12/25 06:00
PMCR- 2010/12/15
CRDT- 2009/12/10 06:00
PHST- 2009/12/10 06:00 [entrez]
PHST- 2009/12/10 06:00 [pubmed]
PHST- 2009/12/25 06:00 [medline]
PHST- 2010/12/15 00:00 [pmc-release]
AID - 00007890-200912150-00011 [pii]
AID - 10.1097/TP.0b013e3181bbee98 [doi]
PST - ppublish
SO  - Transplantation. 2009 Dec 15;88(11):1303-11. doi: 10.1097/TP.0b013e3181bbee98.