Signatures of human regulatory T cells: an encounter with old friends and new players.
BACKGROUND
Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined.


RESULTS
To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function.


CONCLUSIONS
The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.
Pfoertner
Susanne
S
Department of Mucosal Immunity, German Research Centre for Biotechnology, Braunschweig, Germany.
Jeron
Andreas
A
Probst-Kepper
Michael
M
Guzman
Carlos A
CA
Hansen
Wiebke
W
Westendorf
Astrid M
AM
Toepfer
Tanja
T
Schrader
Andres J
AJ
Franzke
Anke
A
Buer
Jan
J
Geffers
Robert
R
D000328:Adult; D017209:Apoptosis; D015551:Autoimmunity / Q000235:genetics; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002470:Cell Survival; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D053645:Interleukin-2 Receptor alpha Subunit