Research

Signatures of human regulatory T cells: an encounter with old friends and new players

Susanne Pfoertner¹ , Andreas Jeron¹ , Michael Probst-Kepper² , Carlos A Guzman³ , Wiebke Hansen¹ , Astrid M Westendorf¹ , Tanja Toepfer¹ , Andres J Schrader⁴ , Anke Franzke⁵ , Jan Buer^1,6 and Robert Geffers¹

¹Department of Mucosal Immunity, German Research Centre for Biotechnology, Braunschweig, Germany

²Volkswagen Foundation Junior Research Group, Department of Visceral and Transplant Surgery, Hanover Medical School, Hanover, Germany

³Department of Vaccinology, German Research Centre for Biotechnology, Braunschweig, Germany

⁴Department of Urology, Philipps-University Medical School, Marburg, Germany

⁵Department of Hematology and Oncology, Hanover Medical School, Hanover, Germany

⁶Institute of Medical Microbiology, Hanover Medical School, Hanover, Germany

author email corresponding author email

Genome Biology 2006, 7:R54doi:10.1186/gb-2006-7-7-r54

Published:	12 July 2006

Subject areas: Immunology, Genome studies

Abstract

Background

Naturally occurring CD4⁺CD25⁺ regulatory T cells (T_Reg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on T_Reg 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 T_Reg cells, we compiled a unique microarray consisting of 350 T_Reg cell associated genes (Human T_Reg Chip) based on whole genome transcription data from human and mouse T_Reg cells. T_Reg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in T_Reg 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 T_Reg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human T_Reg 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 T_Reg cell function.

Conclusion

The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human T_Reg cells. The Human T_Reg 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 T_Reg cells under physiologic and diseased conditions.